How Important is the Metal-free Catalytic Knoevenagel Reaction in
Medicinal Chemistry? An Updated Review

Suzaimi      Johari; Mohd   Rafie   Johan; Nader   Ghaffari   Khaligh

doi:10.2174/0109298673260463231122074253

Abstract

The Knoevenagel condensation is a powerful and primary step for the development of carbon-carbon bond transformations. These condensations offer versatile products/ intermediates for diverse uses in polymers, cosmetics, chemical industries, and medicinal chemistry. Various homogenous and heterogenous catalysts have been found to promote the Knoevenagel condensation reaction, both environmentally and economically. Due to their attractive use in the production of pharmaceutical drugs, they are proven to be the main force that drives the synthesis involving numerous multi-component and multistep reactions. The present study, therefore, aims to summarise reported Knoevenagel condensation reactions using metal-free catalysts resulting in pharmaceutically useful compounds with anti-cancer, anti-tumor, anti-oxidant, anti-malarial, anti-diabetic, and anti- bacterial activities. By considering factors like their structure-activity relationships (SARs), the reaction conditions, and the steps involved, as well as the advantages and limitations of the particular approach, we also provide a general framework and direction in order to achieve superior characteristics of the catalyst.

Keywords: Knoevenagel condensation, anticancer, antibacterial, antioxidant, antivirus, antidiabetic.

« Previous Next »

Zhang Z.; Nie X.; Wang F.; Chen G.; Huang W.Q.; Xia L.; Zhang W.J.; Hao Z.Y.; Hong C.Y.; Wang L.H.; You Y.Z.; Rhodanine-based Knoevenagel reaction and ring-opening polymerization for efficiently constructing multicyclic polymers. Nat Commun 2020,11(1),3654 10.1038/s41467-020-17474-0 32694628 Long N.; Le Gresley A.; Wren S.P.; Thiazolidinediones: An in-depth study of their synthesis and application to medicinal chemistry in the treatment of diabetes mellitus. ChemMedChem 2021,16(11),1717-1736 10.1002/cmdc.202100177 33844475 Bora D.; Kaushal A.; Shankaraiah N.; Anticancer potential of spirocompounds in medicinal chemistry: A pentennial expedition. Eur J Med Chem 2021,215,113263 10.1016/j.ejmech.2021.113263 33601313 Dhakshinamoorthy A.; Jacob M.; Vignesh N.S.; Varalakshmi P.; Pristine and modified chitosan as solid catalysts for catalysis and biodiesel production: A minireview. Int J Biol Macromol 2021,167,807-833 10.1016/j.ijbiomac.2020.10.216 33144253 Veerakumar P; Thanasekaran P; Subburaj T; Lin K-C; A metal-free carbon-based catalyst: An overview and directions for future research. C 2018,4(4),54 10.3390/c4040054 Johari S.; Johan M.R.; Khaligh N.G.; An overview of metal-free sustainable nitrogen-based catalytic knoevenagel condensation reaction. Org Biomol Chem 2022,20(11),2164-2186 10.1039/D2OB00135G 35225313 Badiger K.B.; Kamanna K.; Knoevenagel condensation reaction catalysed by agro-waste extract as a greener solvent catalyst. Organic Communications 2021,14(1),81-91 10.25135/acg.oc.99.21.01.1948 Tokala R.; Bora D.; Shankaraiah N.; Contribution of knoevenagel condensation products toward the development of anticancer agents: An updated review. ChemMedChem 2022,17(8),e202100736 10.1002/cmdc.202100736 35226798 Heravi MM.; Janati F.; Zadsirjan, V Applications of Knoevenagel condensation reaction in the total synthesis of natural products. Monatshefte Für Chemie - Chem. Mon 2020,151,439-482 10.1007/s00706-020-02586-6 Johari S.; Zaharani L.; Gorjian H.; Johan M.R.; Khaligh N.G.; A novel sublimable organic salt: Synthesis, characterization, thermal behavior, and catalytic activity for the synthesis of arylidene, heteroarylidene, and alkylidene malonates. Res Chem Intermed 2022,48(1),361-377 10.1007/s11164-021-04587-4 Hassanzadeh F.; Daneshvar N.; Shirini F.; Mamaghani M.; Introduction of a new bis-derivative of succinimide (Bis-Su) as a sustainable and efficient basic organo-catalyst for the synthesis of arylidene malononitrile and tetrahydrobenzo[b]pyran derivatives under green conditions. Res Chem Intermed 2020,46(11),4971-4984 10.1007/s11164-020-04235-3 van Schijndel J.; Canalle L.A.; Molendijk D.; Meuldijk J.; The green Knoevenagel condensation: solvent-free condensation of benzaldehydes. Green Chem Lett Rev 2017,10(4),404-411 10.1080/17518253.2017.1391881 Sahu P.K.; Sahu P.K.; Kaurav M.S.; Messali M.; Almutairi S.M.; Sahu P.L.; Agarwal D.D.; Metal-free construction of fused pyrimidines via consecutive C–C and C–N bond formation in water. ACS Omega 2018,3(11),15035-15042 10.1021/acsomega.8b01993 31458170 Sadjadi S.; Koohestani F.; Bentonite with high loading of ionic liquid: A potent non-metallic catalyst for the synthesis of dihydropyrimidinones. J Mol Liq 2020,319,114393 10.1016/j.molliq.2020.114393 Nayl A.A.; Arafa W.A.A.; Ahmed I.M.; Abd-Elhamid A.I.; El-Fakharany E.M.; Abdelgawad M.A.; Gomha S.M.; Ibrahim H.M.; Aly A.A.; Bräse S.; Mourad A.K.; Novel pyridinium based ionic liquid promoter for aqueous knoevenagel condensation: Green and efficient synthesis of new derivatives with their anticancer evaluation. Molecules 2022,27(9),2940 10.3390/molecules27092940 35566291 Smith E.L.; Abbott A.P.; Ryder K.S.; Deep eutectic solvents (DESs) and their applications. Chem Rev 2014,114(21),11060-11082 10.1021/cr300162p 25300631 Liu P.; Hao J.W.; Mo L.P.; Zhang Z.H.; Recent advances in the application of deep eutectic solvents as sustainable media as well as catalysts in organic reactions. RSC Advances 2015,5(60),48675-48704 10.1039/C5RA05746A Srivastava S.; Knoevenagel condensation and michael addition in bio‐renewable deep eutectic solvent: facile synthesis of a library of bis‐enol derivatives. ChemistrySelect 2020,5(2),799-803 10.1002/slct.201904806 Wang Y.; Yao Q.X.; He J.R.; Liang Z.H.; Li X.; Cheng H.; Li L-L.; L-proline-catalyzed Knoevenagel reaction promoted by choline chloride-based deep eutectic solvents. Biomass Convers Biorefin 2022,12(S1),87-93 10.1007/s13399-021-01747-9 Navudu R.; Mannem G.R.; Margani T.; Rao Vanga U.M.; Bollikolla H.B.; Synthesis, anticancer and antioxidant evaluation of some new 2-Aryl and 2-Pyrazole-2,3-dihydroquinazolin-4(1H)-ones. Asian J Chem 2016,28(6),1321-1324 10.14233/ajchem.2016.19676 Guchhait S.K.; Sisodiya S.; Saini M.; Shah Y.V.; Kumar G.; Daniel D.P.; Hura N.; Chaudhary V.; Synthesis of polyfunctionalized pyrroles via a tandem reaction of michael addition and intramolecular cyanide-mediated nitrile-to-nitrile condensation. J Org Chem 2018,83(10),5807-5815 10.1021/acs.joc.8b00465 29671317 Porter D.W.; Bradley M.; Brown Z.; Charlton S.J.; Cox B.; Hunt P.; Janus D.; Lewis S.; Oakley P.; O’Connor D.; Reilly J.; Smith N.; Press N.J.; The discovery of potent, orally bioavailable pyrimidine-5-carbonitrile-6-alkyl CXCR2 receptor antagonists. Bioorg Med Chem Lett 2014,24(15),3285-3290 10.1016/j.bmcl.2014.06.011 24974342 Ata A.; Synthesis and biological evaluation of benzothiazole derivatives of pyrimidines, acrylonitriles, and coumarins. Heterocycles 2006,68,347 10.3987/COM-05-10609 Bolikolla H.B.; Merugu S.K.; Improved knoevenagel condensation protocol for the synthesis of cyanoacrylates and their anticancer activity. J Mex Chem Soc 2023,67(1),60-69 10.29356/jmcs.v67i1.1835 Jadhav C.K.; Nipate A.S.; Chate A.V.; Dofe V.S.; Sangshetti J.N.; Khedkar V.M.; Gill C.H.; Rapid construction of substituted dihydrothiophene ureidoformamides at room temperature using diisopropyl ethyl ammonium acetate: A green perspective. ACS Omega 2020,5(45),29055-29067 10.1021/acsomega.0c03575 33225136 Onteddu R.S.; Mutchu R.B.; Thripuram D.V.; Chandu B.; Chavakula L.R.; Golkonda R.M.; Kotra V.; Bollikolla B.H.; Synthesis and anticancer activity of some new 2‐benzyloxy‐5‐alkyne substituted pyrimidines: An application to sonogashira coupling. ChemistrySelect 2020,5(27),8194-8197 10.1002/slct.202001668 Jadhav C.K.; Nipate A.S.; Chate A.V.; Songire V.D.; Patil A.P.; Gill C.H.; Efficient rapid access to biginelli for the multicomponent synthesis of 1,2,3,4-tetrahydropyrimidines in room-temperature diisopropyl ethyl ammonium acetate. ACS Omega 2019,4(27),22313-22324 10.1021/acsomega.9b02286 31909314 Sui G.; Li T.; Zhang B.; Wang R.; Hao H.; Zhou W.; Recent advances on synthesis and biological activities of aurones. Bioorg Med Chem 2021,29,115895 10.1016/j.bmc.2020.115895 33271454 Mazziotti I.; Petrarolo G.; La Motta C.; Aurones: A golden resource for active compounds. Molecules 2021,27(1),2 10.3390/molecules27010002 35011233 Alsayari A.; Muhsinah A.B.; Hassan M.Z.; Ahsan M.J.; Alshehri J.A.; Begum N.; Aurone: A biologically attractive scaffold as anticancer agent. Eur J Med Chem 2019,166,417-431 10.1016/j.ejmech.2019.01.078 30739824 Popova A.V.; Bondarenko S.P.; Frasinyuk M.S.; Aurones: Synthesis and properties. Chem Heterocycl Compd 2019,55(4-5),285-299 10.1007/s10593-019-02457-x Hassan G.S.; Georgey H.H.; George R.F.; Mohamed E.R.; Aurones and furoaurones: Biological activities and synthesis. Bull Fac Pharm Cairo Univ 2018,56(2),121-127 10.1016/j.bfopcu.2018.06.002 Harkat H.; Weibel J.; Pale P.; Chimie I; De ; Uni V.; Pasteur L; Versatile and expeditious synthesis of aurones via Au I-catalyzed cyclization. J Org Chem 2008,73(4),1620-1623 Taylor C.; Bolshan Y.; Metal-free methodology for the preparation of sterically hindered alkynoylphenols and its application to the synthesis of flavones and aurones. Tetrahedron Lett 2015,56(29),4392-4396 10.1016/j.tetlet.2015.05.097 Karadendrou M.A.; Kostopoulou I.; Kakokefalou V.; Tzani A.; Detsi A.; L-proline-based natural deep eutectic solvents as efficient solvents and catalysts for the ultrasound-assisted synthesis of aurones via knoevenagel condensation. Catalysts 2022,12(3),249 10.3390/catal12030249 Jeon R.; Park S.; Synthesis and biological activity of Benzoxazole containing thiazolidinedione derivatives. Arch Pharm Res 2004,27(11),1099-1105 10.1007/BF02975111 15595409 Bireddy S.R.; Konkala V.S.; Godugu C.; Dubey P.K.; A review on the synthesis and biological studies of 2,4-thiazolidinedione derivatives. Mini Rev Org Chem 2020,17(8),958-974 10.2174/1570193X17666200221123633 Nastasă C.; Tiperciuc B.; Pârvu A.; Duma M.; Ionuţ I.; Oniga O.; Synthesis of new N-substituted 5-arylidene-2,4-thiazolidinediones as anti-inflammatory and antimicrobial agents. Arch Pharm 2013,346(6),481-490 10.1002/ardp.201300021 23666636 Maccari R.; Ottanà R.; Ciurleo R.; Vigorita M.G.; Rakowitz D.; Steindl T.; Langer T.; Evaluation of in vitro aldose redutase inhibitory activity of 5-arylidene-2,4-thiazolidinediones. Bioorg Med Chem Lett 2007,17(14),3886-3893 10.1016/j.bmcl.2007.04.109 17512196 Steinrück H.P.; Wasserscheid P.; Ionic liquids in catalysis. Catal Lett 2015,145(1),380-397 10.1007/s10562-014-1435-x McNeice P.; Marr P.C.; Marr A.C.; Basic ionic liquids for catalysis: The road to greater stability. Catal Sci Technol 2021,11(3),726-741 10.1039/D0CY02274H Singh S.K.; Savoy A.W.; Ionic liquids synthesis and applications: An overview. J Mol Liq 2019,297,110238 10.1016/j.molliq.2019.112038 Nasirpour N.; Mohammadpourfard M.; Zeinali Heris S.; Ionic liquids: Promising compounds for sustainable chemical processes and applications. Chem Eng Res Des 2020,160,264-300 10.1016/j.cherd.2020.06.006 Talegaonkar R; Mohammad N; Ionic liquid mediated synthesis of 5-arylidine-2 , 4- thiazolidinedionesand antibacterial evaluation. 2022,10,56-60 Thorat B.R.; Nagre D.T.; Dhurandhar P.P.; Borase P.K.; Bavkar S.; Kasar R.R.; Narkar R.D.; Farooqui M.; Mali S.N.; L-proline catalyzed knoevenagel condensation of aldehydes with active methylene compounds and their molecular modeling studies for anti-SARS CoV-2 potentials. Curr Enzym Inhib 2022,18(2),145-159 10.2174/1573408018666220516104525 Mohammadi Ziarani G.; Moradi R.; Ahmadi T.; Gholamzadeh P.; The molecular diversity scope of 4-hydroxycoumarin in the synthesis of heterocyclic compounds via multicomponent reactions. Mol Divers 2019,23(4),1029-1064 10.1007/s11030-019-09918-7 30697671 Gill R.K.; Rawal R.K.; Bariwal J.; Recent advances in the chemistry and biology of benzothiazoles. Arch Pharm 2015,348(3),155-178 10.1002/ardp.201400340 25682746 Irfan A.; Batool F.; Zahra Naqvi S.A.; Islam A.; Osman S.M.; Nocentini A.; Alissa S.A.; Supuran C.T.; Benzothiazole derivatives as anticancer agents. J Enzyme Inhib Med Chem 2020,35(1),265-279 10.1080/14756366.2019.1698036 31790602 Sunderhaus J.D.; Martin S.F.; Applications of multicomponent reactions to the synthesis of diverse heterocyclic scaffolds. Chemistry 2009,15(6),1300-1308 10.1002/chem.200802140 19132705 Malinakova H.; Recent advances in the discovery and design of multicomponent reactions for the generation of small-molecule libraries. Reports Org Chem 2015,75,75 10.2147/ROC.S65115 Kadam P.R.; Bodke Y.D.; Naik M.D.; Nagaraja O.; Manjunatha B.; One-pot three-component synthesis of thioether linked 4-hydroxycoumarin-benzothiazole derivatives under ambient condition and evaluation of their biological activity. Results Chem 2022,4,100303 10.1016/j.rechem.2022.100303 Patil V.; Tilekar K.; Mehendale-Munj S.; Mohan R.; Ramaa C.S.; Synthesis and primary cytotoxicity evaluation of new 5-benzylidene-2,4-thiazolidinedione derivatives. Eur J Med Chem 2010,45(10),4539-4544 10.1016/j.ejmech.2010.07.014 20667627 Havrylyuk D.; Zimenkovsky B.; Vasylenko O.; Day C.W.; Smee D.F.; Grellier P.; Lesyk R.; Synthesis and biological activity evaluation of 5-pyrazoline substituted 4-thiazolidinones. Eur J Med Chem 2013,66,228-237 10.1016/j.ejmech.2013.05.044 23811085 Alegaon S.G.; Alagawadi K.R.; New thiazolidinedione-5-acetic acid amide derivatives: Synthesis, characterization and investigation of antimicrobial and cytotoxic properties. Med Chem Res 2012,21(6),816-824 10.1007/s00044-011-9598-0 Zimenkovskii B.S.; Kutsyk R.V.; Lesyk R.B.; Matyichuk V.S.; Obushak N.D.; Klyufinska T.I.; Synthesis and antimicrobial activity of 2,4-dioxothiazolidine-5-acetic acid amides. Pharm Chem J 2006,40(6),303-306 10.1007/s11094-006-0115-6 Rakowitz D.; Maccari R.; Ottanà R.; Vigorita M.G.; In vitro aldose reductase inhibitory activity of 5-benzyl-2,4-thiazolidinediones. Bioorg Med Chem 2006,14(2),567-574 10.1016/j.bmc.2005.08.056 16202614 Sucheta T.S.; Tahlan S.; Verma P.K.; Biological potential of thiazolidinedione derivatives of synthetic origin. Chem Cent J 2017,11(1),130 10.1186/s13065-017-0357-2 29222671 Kumar P.; Asati V.; Choubey A.; Synthesis and characterization of novel 3-(aminomethyl)5-benzylidenethiazolin-dine-2,4-dione derivatives as anticancer agents. Int J Adv Sci Res 2021,12(4),154-164 10.55218/JASR.202112420 Kaur R.; Kumar R.; Dogra N.; Kumar A.; Yadav A.K.; Kumar M.; Synthesis and studies of thiazolidinedione–isatin hybrids as α-glucosidase inhibitors for management of diabetes. Future Med Chem 2021,13(5),457-485 10.4155/fmc-2020-0022 33506699 El-Naggar M.; Eldehna W.; Almahli H.; Elgez A.; Fares M.; Elaasser M.; Abdel-Aziz H.; Novel thiazolidinone/thiazolo[3,2-a]benzimidazolone-isatin conjugates as apoptotic anti-proliferative agents towards breast cancer: One-pot synthesis and in vitro biological evaluation. Molecules 2018,23(6),1420 10.3390/molecules23061420 29895744 Hamzehloueian M.; Sarrafi Y.; Darroudi M.; Arani M.A.; Darestani R.N.; Safari F.; Synthesis, antibacterial and anticancer activities evaluation of new 4-thiazolidinone-indolin-2-one analogs. Biointerface Res Appl Chem 2021,12(6),8094-8104 10.33263/BRIAC126.80948104 Zhang R.R.; Liu J.; Zhang Y.; Hou M.Q.; Zhang M.Z.; Zhou F.; Zhang W.H.; Microwave-assisted synthesis and antifungal activity of novel coumarin derivatives: Pyrano[3,2- c]chromene-2,5-diones. Eur J Med Chem 2016,116,76-83 10.1016/j.ejmech.2016.03.069 27060759 Yavari I.; Askarian-Amiri M.; A synthesis of spiroindolo[2,1- b]quinazoline-6,2′-pyrido[2,1- b][1,3]oxazines from tryptanthrins and huisgen zwitterions. Synth Commun 2021,51,1-7 10.1080/00397911.2021.1899237 Kaur R.; Manjal S.K.; Rawal R.K.; Kumar K.; Recent synthetic and medicinal perspectives of tryptanthrin. Bioorg Med Chem 2017,25(17),4533-4552 10.1016/j.bmc.2017.07.003 28720329 Sadeghian Z.; Bayat M.; Safari F.; Synthesis and antitumor activity screening of spiro tryptanthrin-based heterocyclic compounds. Med Chem Res 2022,31(3),497-506 10.1007/s00044-022-02856-4 Araghi R.; Mirjalili B.B.F.; Zamani L.; Khabnadideh S.; Zomoridian K.; Faghih Z.; Arabi H.; Docking, synthesis and evaluation of the antifungal activity of pyrimido[4,5-b]quinolins. Iran J Pharm Res 2020,19(1),251-259 10.22037/ijpr.2020.1101010 32922484 Ranjbar S.; Edraki N.; Firuzi O.; Khoshneviszadeh M.; Miri R.; 5-Oxo-hexahydroquinoline: An attractive scaffold with diverse biological activities. Mol Divers 2019,23(2),471-508 10.1007/s11030-018-9886-4 30390186 Eghtedari M.; Azimzadeh Arani M.; Sarrafi Y.; Shafiei M.; Alimohammadi K.; Safari F.; Foroumadi A.; Synthesis and antitumor activity evaluation of novel pyrimidoquinoline derivatives. Polycycl Aromat Compd 2022,42(7),4359-4373 10.1080/10406638.2021.1892778 Küpeli Akkol E.; Genç Y.; Karpuz B.; Sobarzo-Sánchez E.; Capasso R.; Coumarins and coumarin-related compounds in pharmacotherapy of cancer. Cancers 2020,12(7),1959 10.3390/cancers12071959 32707666 Song X.F.; Fan J.; Liu L.; Liu X.F.; Gao F.; Coumarin derivatives with anticancer activities: An update. Arch Pharm 2020,353(8),2000025 10.1002/ardp.202000025 32383190 Gaber A.; Alsanie W.F.; Alhomrani M.; Alamri A.S.; El-Deen I.M.; Refat M.S.; Synthesis and characterization of some new coumarin derivatives as probable breast anticancer mcf-7 drugs. Crystals 2021,11(5),565 10.3390/cryst11050565 Pandey J.; Prajapati P.; Srivastava A.; Tandon P.; Sinha K.; Ayala A.P.; Bansal A.K.; Spectroscopic and molecular structure (monomeric and dimeric model) investigation of Febuxostat: A combined experimental and theoretical study. Spectrochim Acta A Mol Biomol Spectrosc 2018,203,1-12 10.1016/j.saa.2018.05.074 29852375 Pandey A.; Pandey A.; Dubey R.; Kant R.; Pandey J.; Synthesis and computational studies of potent antimicrobial and anticancer indolone scaffolds with spiro cyclopropyl moiety as a novel design element. J Indian Chem Soc 2022,99(7),100539 10.1016/j.jics.2022.100539 Sharma P.K.; Sharma H.P.; Chakole C.M.; Pandey J.; Chauhan M.K.; Application of vitamin E TPGS in ocular therapeutics - attributes beyond excipient. J Indian Chem Soc 2022,99(3),100387 10.1016/j.jics.2022.100387 Pandey A.; Dubey R.; Ravikant ; Pandey J.; Synthesis of uniquely substituted 4H-Chromeno[2,3-d] pyrimidin-2-one derivatives by l-Proline catalyzed green chemistry method. J Indian Chem Soc 2023,100(1),100862 10.1016/j.jics.2022.100862 Pratap R.; Ram V.J.; Natural and synthetic chromenes, fused chromenes, and versatility of dihydrobenzo[h]chromenes in organic synthesis. Chem Rev 2014,114(20),10476-10526 10.1021/cr500075s 25303539 Tanaka H.; Atsumi I.; Shirota O.; Sekita S.; Sakai E.; Sato M.; Murata J.; Murata H.; Darnaedi D.; Chen I.S.; Three new constituents from the roots of Erythrina variegata and their antibacterial activity against methicillin-resistant Staphylococcus aureus. Chem Biodivers 2011,8(3),476-482 10.1002/cbdv.201000068 21404431 Itokawa H.; Ibraheim Z.Z.; Qiao Y.F.; Takeya K.; Anthraquinones, naphthohydroquinones and naphthohydroquinone dimers from Rubia cordifolia and their cytotoxic activity. Chem Pharm Bull 1993,41(10),1869-1872 10.1248/cpb.41.1869 8281583 Khurana JM.; Nand B.; Saluja, P1, 8-Diazabicyclo [5. 4. 0] undec-7-ene: A highly efficient catalyst for one-pot synthesis of substituted tetrahydro-4 H-chromenes, tetrahydro [b] pyrans, pyrano [d] pyrimidines, and 4H-pyrans in aqueous medium. J Heterocycl Chem 2014,51(3),618-624 Thangamani A.; Grindstone chemistry: An efficient and green synthesis of 2-amino-4H-benzo[b]pyrans. J Appl Adv Res 2017,2,78-85 10.21839/jaar.2017.v2i2.65 Zanin L.L.; Jimenez D.E.Q.; de Jesus M.P.; Diniz L.F.; Ellena J.; Porto A.L.M.; Synthesis and X-ray crystal structures of polyfunctionalized 4H-chromene derivatives via tricomponent reaction with Knoevenagel adducts as intermediates in aqueous medium. J Mol Struct 2021,1223,129226 10.1016/j.molstruc.2020.129226 Strugstad M.; Despotovski S.; A summary of extraction, synthesis, properties, and potential uses of juglone: A literature review. BC J Ecosyst Manag 2013,13(3),1-16 10.22230/jem.2012v13n3a119 Tang Y.T.; Li Y.; Chu P.; Ma X.D.; Tang Z.Y.; Sun Z.L.; Molecular biological mechanism of action in cancer therapies: Juglone and its derivatives, the future of development. Biomed Pharmacother 2022,148,112785 10.1016/j.biopha.2022.112785 35272138 Lozynskyi A.V.; Kaminskyy D.V.; Romanchyshyn K.B.; Semenciv N.G.; Ogurtsov V.V.; Nektegayev I.O.; Lesyk R.B.; Screening of antioxidant and anti-inflammatory activities among thiopyrano[2,3-d]thiazoles. Biopolim Kletka 2015,31(2),131-137 10.7124/bc.0008D8 Kryshchyshyn A.; Roman O.; Lozynskyi A.; Lesyk R.; Thiopyrano[2,3-d]thiazoles as new efficient scaffolds in medicinal chemistry. Sci Pharm 2018,86(2),26 10.3390/scipharm86020026 29903979 Lozynskyi A.; Golota S.; Zimenkovsky B.; Atamanyuk D.; Gzella A.; Lesyk R.; Synthesis, anticancer and antiviral activities of novel thiopyrano[2,3-d]thiazole-6-carbalde-hydes. Phosphorus Sulfur Silicon Relat Elem 2016,191(9),1245-1249 10.1080/10426507.2016.1166108 Ivasechko I.; Lozynskyi A.; Senkiv J.; Roszczenko P.; Kozak Y.; Finiuk N.; Klyuchivska O.; Kashchak N.; Manko N.; Maslyak Z.; Lesyk D.; Karkhut A.; Polovkovych S.; Czarnomysy R.; Szewczyk O.; Kozytskiy A.; Karpenko O.; Khyluk D.; Gzella A.; Bielawski K.; Bielawska A.; Dzubak P.; Gurska S.; Hajduch M.; Stoika R.; Lesyk R.; Molecular design, synthesis and anticancer activity of new thiopyrano[2,3-d]thiazoles based on 5-hydroxy-1,4-naphthoquinone (juglone). Eur J Med Chem 2023,252,115304 10.1016/j.ejmech.2023.115304 37001390 Mhiri C.; Boubakri L.; Ternane R.; Mansour L.; Harrath A.H.; Al-Tamimi J.; Baklouti L.; Hamdi N.; Three‐component, one‐pot synthesis of pyrano[3,2‐c]chromene derivatives catalyzed by ammonium acetate: Synthesis, characterization, cation binding, and biological determination. J Heterocycl Chem 2020,57(1),291-298 10.1002/jhet.3776 Baitha A.; Gopinathan A.; Krishnan K.; Dabholkar V.V.; Synthesis of 2‐amino‐4‐(2‐ethoxybenzo[d][1,3]dioxol‐5‐yl)‐4H‐pyran‐3‐carbonitrile derivatives and their biological evaluation. J Heterocycl Chem 2018,55(5),1189-1192 10.1002/jhet.3152 Zheng J.; He M.; Xie B.; Yang L.; Hu Z.; Zhou H.B.; Dong C.; Enantioselective synthesis of novel pyrano[3,2- c]chromene derivatives as AChE inhibitors via an organocatalytic domino reaction. Org Biomol Chem 2018,16(3),472-479 10.1039/C7OB02794J 29265146 Raj V.; Lee J.; 2H/4H-Chromenes-A versatile biologically attractive scaffold. Front Chem 2020,8,623 10.3389/fchem.2020.00623 Yousefi M.R.; Goli-Jolodar O.; Shirini F.; Piperazine: An excellent catalyst for the synthesis of 2-amino-3-cyano-4H-pyrans derivatives in aqueous medium. Bioorg Chem 2018,81,326-333 10.1016/j.bioorg.2018.08.026 30179795 Gardelly M.; Trimech B.; Belkacem M.A.; Harbach M.; Abdelwahed S.; Mosbah A.; Bouajila J.; Ben Jannet H.; Synthesis of novel diazaphosphinanes coumarin derivatives with promoted cytotoxic and anti-tyrosinase activities. Bioorg Med Chem Lett 2016,26(10),2450-2454 10.1016/j.bmcl.2016.03.108 27080182 Tashrifi Z.; Mohammadi-Khanaposhtani M.; Hamedifar H.; Larijani B.; Ansari S.; Mahdavi M.; Synthesis and pharmacological properties of polysubstituted 2-amino-4H-pyran-3-carbonitrile derivatives. Mol Divers 2020,24(4),1385-1431 10.1007/s11030-019-09994-9 31555954 Nongrum R.; Nongthombam G.S.; Kharkongor M.; Star Rani J.W.; Rahman N.; Kathing C.; Myrboh B.; Nongkhlaw R.; A nano-organo catalyzed route towards the efficient synthesis of benzo[b]pyran derivatives under ultrasonic irradiation. RSC Advances 2016,6(110),108384-108392 10.1039/C6RA24108E Gholamhosseini-Nazari M.; Esmati S.; Safa K.D.; Khataee A.; Teimuri-Mofrad R.; Fe3O4@SiO2-BenzIm-Fc[Cl]/ZnCl2: A novel and efficient nano-catalyst for the one-pot three-component synthesis of pyran annulated bis-heterocyclic scaffolds under ultrasound irradiation. Res Chem Intermed 2019,45(4),1841-1862 10.1007/s11164-018-3704-6 Rayadurgam J.; Sabbasani, RR Synthesis of D-ribose and D-galactose derived chiral ionic liquids as recyclable chiral solvent for michael addition reaction. Trends Carbohydr Res 2015,7,60-67 Garg P.; Reddy S.R.; Biomass‐derived sugar ionic liquid as a sustainable organocatalyst: An efficient synthesis of functionalized dihydropyrano coumarins. Asian J Org Chem 2022,11(9),e202200322 10.1002/ajoc.202200322 Mohamadpour F.; Visible light irradiation promoted catalyst-free and solvent-free synthesis of pyrano[2,3-d]pyrimidine scaffolds at room temperature. J Saudi Chem Soc 2020,24(8),636-641 10.1016/j.jscs.2020.06.006 Brahmachari G.; Nurjamal K.; Ultrasound-assisted and trisodium citrate dihydrate-catalyzed green protocol for efficient and one-pot synthesis of substituted chromeno[3′,4′:5,6]pyrano[2,3-d]pyrimidines at ambient conditions. Tetrahedron Lett 2019,60(29),1904-1908 10.1016/j.tetlet.2019.06.028 Khumalo M.R.; Maddila S.N.; Maddila S.; Jonnalagadda S.B.; A facile and one-pot synthesis of new tetrahydrobenzo[b]pyrans in water under microwave irradiation. BMC Chem 2019,13(1),132 10.1186/s13065-019-0651-2 31788672 Aminkhani A.; Talati M.; Sharifi R.; Chalabian F.; Katouzian F.; Highly efficient one‐pot three‐component synthesis and antimicrobial activity of 2‐amino‐4 H ‐chromene derivatives. J Heterocycl Chem 2019,56(6),1812-1819 10.1002/jhet.3555 Adibian F.; Pourali A.R.; Maleki B.; Baghayeri M.; Amiri A.; One‐pot synthesis of dihydro-1H-indeno[1,2-b] pyridines and tetrahydrobenzo[b] pyran derivatives using a new and efficient nanocomposite catalyst based on N‐butylsulfonate‐functionalized MMWCNTs-D-NH2. Polyhedron 2020,175,114179 10.1016/j.poly.2019.114179 Mahmoudi Z.; Ghasemzadeh M.A.; Kabiri-Fard H.; Fabrication of UiO-66 nanocages confined Brønsted ionic liquids as an efficient catalyst for the synthesis of dihydropyrazolo[4′,3′:5,6]pyrano[2,3-d]pyrimidines. J Mol Struct 2019,1194,1-10 10.1016/j.molstruc.2019.05.079 Koohestani F.; Sadjadi S.; Polyionic liquid decorated chitosan beads as versatile metal-free catalysts for catalyzing chemical reactions in aqueous media. J Mol Liq 2021,334,115754 10.1016/j.molliq.2021.115754 Nahar L.; Talukdar A.D.; Nath D.; Nath S.; Mehan A.; Ismail F.M.D.; Sarker S.D.; Naturally occurring calanolides: Occurrence, biosynthesis, and pharmacological properties including therapeutic potential. Molecules 2020,25(21),4983 10.3390/molecules25214983 33126458 Zghab I.; Trimeche B.; Mansour M.B.; Hassine M.; Touboul D.; Jannet H.B.; Regiospecific synthesis, antibacterial and anticoagulant activities of novel isoxazoline chromene derivatives. Arab J Chem 2017,10,S2651-S2658 10.1016/j.arabjc.2013.10.008 El-Agrody A.M.; Halawa A.H.; Fouda A.M.; Al-Dies A.A.M.; The anti-proliferative activity of novel 4H-benzo[h]chromenes, 7H-benzo[h]-chromeno[2,3-d]pyrimi-dines and the structure–activity relationships of the 2-, 3-positions and fused rings at the 2, 3-positions. J Saudi Chem Soc 2017,21(1),82-90 10.1016/j.jscs.2016.03.002 Saczewski J.; Paluchowska A.; Klenc J.; Raux E.; Barnes S.; Sullivan S.; Duszynska B.; Bojarski A.J.; Strekowski L.; Synthesis of 4‐substituted 2‐(4‐methylpiperazino)pyrimidines and quinazoline analogs as serotonin 5‐HT 2A receptor ligands. J Heterocycl Chem 2009,46(6),1259-1265 10.1002/jhet.236 Yao C.; Yu C.; Li T.; Tu S.; An efficient synthesis of 4 H-Benzo[g]chromene-5,10-dione de-rivatives through triethylbenzylammonium chloride catalyzed multicomponent reaction under solvent-free conditions. Chin J Chem 2009,27(10),1989-1994 10.1002/cjoc.200990334 Khurana J.M.; Nand B.; Saluja P.; DBU: A highly efficient catalyst for one-pot synthesis of substituted 3,4-dihydropyrano[3,2-c]chromenes, dihydropyrano[4,3-b]pyranes, 2-amino-4H-benzo[h]chromenes and 2-amino-4H benzo[g]chromenes in aqueous medium. Tetrahedron 2010,66(30),5637-5641 10.1016/j.tet.2010.05.082 Thanh NH; Phuong HT; Giang LNT; Giang NTQ; Ha NTT; Anh DTT; 4-(Dimethylamino)pyridine as an efficient catalyst for one-pot synthesis of 1,4-pyranonaphthoquinone derivatives via microwave-assisted sequential three component reaction in green solvent. Nat Prod Commun 2021,16,1934578X2110539 10.1177/1934578X211053951 Jiang L.; Peng P.; Li M.; Li L.; Zhao M.; Yuan M.; Yuan M.; Efficient synthesis of 3-sulfonyl-2-sulfonylmethyl-2H-chromenes via tandem knoevenagel condensation/oxa-michael addition protocol. Catalysts 2022,12(5),491 10.3390/catal12050491 Kumar A.; Thadkapally S.; Menon R.S.; Base-mediated cyclocondensation of salicylaldehydes and 2-bromoallyl sulfones for the synthesis of 3-sulfonylchromene derivatives and their regioselective friedel–crafts heteroarylation reactions. J Org Chem 2015,80(21),11048-11056 10.1021/acs.joc.5b02324 26465821 Bellucci M.C.; Sacchetti A.; Volonterio A.; Multicomponent approach to libraries of substituted dihydroorotic acid amides. ACS Comb Sci 2019,21(10),705-715 10.1021/acscombsci.9b00144 31454221 Arcadia C.E.; Kennedy E.; Geiser J.; Dombroski A.; Oakley K.; Chen S.L.; Sprague L.; Ozmen M.; Sello J.; Weber P.M.; Reda S.; Rose C.; Kim E.; Rubenstein B.M.; Rosenstein J.K.; Multicomponent molecular memory. Nat Commun 2020,11(1),691 10.1038/s41467-020-14455-1 32019933 Ghashghaei O.; Seghetti F.; Lavilla R.; Selectivity in multiple multicomponent reactions: Types and synthetic applications. Beilstein J Org Chem 2019,15,521-534 10.3762/bjoc.15.46 30873236 Elinson M.N.; Ryzhkova Y.E.; Vereshchagin A.N.; Ryzhkov F.V.; Kalashnikova V.M.; Egorov M.P.; Direct and efficient electrocatalytic multicomponent assembling of arylaldehydes, malononitrile, and pyrazolin-5-ones into spirocyclopropyl pyrazolone scaffold. Monatsh Chem 2021,152(6),641-648 10.1007/s00706-021-02784-w Kuznetcova A.V.; Odin I.S.; Golovanov A.A.; Grigorev I.M.; Vasilyev A.V.; Multicomponent reaction of conjugated enynones with malononitrile and sodium alkoxides: Complex reaction mechanism of the formation of pyridine derivatives. Tetrahedron 2019,75(33),4516-4530 10.1016/j.tet.2019.06.041 Hajra S.; Abu Saleh S.K.; Hazra A.; Singh M.S.; Organocatalytic domino reaction of spiroaziridine oxindoles and malononitrile for the enantiopure synthesis of spiro dihydropyrrole-3,3′-oxindoles. J Org Chem 2019,84(12),8194-8201 10.1021/acs.joc.9b01226 31142119 Saleem F.; Kanwal ; Mohammed Khan K.; Chigurupati S.; Andriani Y.; Solangi M.; Hameed S.; Abdel Monem Abdel Hafez A.; Begum F.; Arif Lodhi M.; Taha M.; Rahim F.; Tengku Muhammad T.S.; Perveen S.; Dicyanoanilines as potential and dual inhibitors of α-amylase and α-glucosidase enzymes: Synthesis, characterization, in vitro, in silico, and kinetics studies. Arab J Chem 2022,15(3),103651 10.1016/j.arabjc.2021.103651 Abaee M.S.; Hatamifard A.; Mojtahedi M.M.; Notash B.; Naderi S.; Pseudo-five-component organocatalyzed synthesis of dicyanoanillines using only malononitrile and aromatic aldehydes. Synth Commun 2022,52(3),346-355 10.1080/00397911.2021.2024573 Alvim H.G.O.; da Silva Júnior E.N.; Neto B.A.D.; What do we know about multicomponent reactions? Mechanisms and trends for the Biginelli, Hantzsch, Mannich, Passerini and Ugi MCRs. RSC Advances 2014,4(97),54282-54299 10.1039/C4RA10651B Dömling A.; Wang W.; Wang K.; Chemistry and biology of multicomponent reactions. Chem Rev 2012,112(6),3083-3135 10.1021/cr100233r 22435608 Bienaymé H.; Hulme C.; Oddon G.; Schmitt P.; Maximizing synthetic efficiency: Multi-component transformations lead the way. Chemistry 2000,6(18),3321-3329 10.1002/1521-3765(20000915)6:18<3321:AID-CHEM3321>3.0.CO;2-A 11039522 Trotsko N.; Przekora A.; Zalewska J.; Ginalska G.; Paneth A.; Wujec M.; Synthesis and in vitro antiproliferative and antibacterial activity of new thiazolidine-2,4-dione derivatives. J Enzyme Inhib Med Chem 2018,33(1),17-24 10.1080/14756366.2017.1387543 29098896 Sindhu J.; Singh H.; Khurana J.M.; Sharma C.; Aneja K.R.; Multicomponent domino process for the synthesis of some novel 5-(arylidene)-3-((1-aryl-1H-1,2,3-triazol-4-yl)methyl)-thiazolidine-2,4-diones using PEG-400 as an efficient reaction medium and their antimicrobial evaluation. Chin Chem Lett 2015,26(1),50-54 10.1016/j.cclet.2014.09.006 Nyaki H.Y.; Mahmoodi N.O.; Synthesis and characterization of derivatives including thiazolidine-2,4-dione/1-H-imidazole and evaluation of antimicrobial, antioxidant, and cytotoxic properties of new synthetic heterocyclic compounds. Res Chem Intermed 2021,47(10),4129-4155 10.1007/s11164-021-04525-4 Sharma P.; Reddy T.S.; Kumar N.P.; Senwar K.R.; Bhargava S.K.; Shankaraiah N.; Conventional and microwave-assisted synthesis of new 1 H -benzimidazole-thiazolidinedione derivatives: A potential anticancer scaffold. Eur J Med Chem 2017,138,234-245 10.1016/j.ejmech.2017.06.035 28668476 Prabhakaran S.; Nivetha N.; Patil S.M.; Mary Martiz R.; Ramu R.; Sreenivasa S.; Velmathi S.; One-pot three-component synthesis of novel phenyl-pyrano-thiazol-2-one derivatives and their anti-diabetic activity studies. Results Chem 2022,4,100439 10.1016/j.rechem.2022.100439 Chadha N.; Bahia M.S.; Kaur M.; Silakari O.; Thiazolidine-2,4-dione derivatives: Programmed chemical weapons for key protein targets of various pathological conditions. Bioorg Med Chem 2015,23(13),2953-2974 10.1016/j.bmc.2015.03.071 25890697 da Rocha Junior L.F.; de Melo Rêgo M.J.B.; Cavalcanti M.B.; Pereira M.C.; Pitta M.G.R.; de Oliveira P.S.S.; Gonçalves S.M.C.; Duarte A.L.B.P.; de Lima M.C.A.; Pitta I.R.; Pitta M.G.R.; Synthesis of a novel thiazolidinedione and evaluation of its modulatory effect on IFN- γ, IL-6, IL-17A, and IL-22 production in PBMCs from rheumatoid arthritis patients. BioMed Res Int 2013,2013,1-8 10.1155/2013/926060 24078927 Youssef A.M.; Sydney White M.; Villanueva E.B.; El-Ashmawy I.M.; Klegeris A.; Synthesis and biological evaluation of novel pyrazolyl-2,4-thiazolidinediones as anti-inflammatory and neuroprotective agents. Bioorg Med Chem 2010,18(5),2019-2028 10.1016/j.bmc.2010.01.021 20138770 Kavetsou E.; Gkionis L.; Galani G.; Gkolfinopoulou C.; Argyri L.; Pontiki E.; Chroni A.; Hadjipavlou-Litina D.; Detsi A.; Synthesis of prenyloxy coumarin analogues and evaluation of their antioxidant, lipoxygenase (LOX) inhibitory and cytotoxic activity. Med Chem Res 2017,26(4),856-866 10.1007/s00044-017-1800-6 Chatterjee B.; Sharma A.; Fruit enzymes and their application: A review. Int J Clin Biomed Res 2018,4(2),84 10.5455/ijcbr.2018.42.18 Lončarić M.; Strelec I.; Pavić V.; Rastija V.; Karnaš M.; Molnar M.; Green synthesis of thiazolidine-2,4-dione derivatives and their lipoxygenase inhibition activity with QSAR and molecular docking studies. Front Chem 2022,10,912822 10.3389/fchem.2022.912822 35864866 Medina F.G.; Marrero J.G.; Macías-Alonso M.; González M.C.; Córdova-Guerrero I.; Teissier García A.G.; Osegueda-Robles S.; Coumarin heterocyclic derivatives: Chemical synthesis and biological activity. Nat Prod Rep 2015,32(10),1472-1507 10.1039/C4NP00162A 26151411 Barot K.P.; Jain S.V.; Kremer L.; Singh S.; Ghate M.D.; Recent advances and therapeutic journey of coumarins: Current status and perspectives. Med Chem Res 2015,24(7),2771-2798 10.1007/s00044-015-1350-8 Borges F.; Roleira F.; Milhazes N.; Santana L.; Uriarte E.; Simple coumarins and analogues in medicinal chemistry: Occurrence, synthesis and biological activity. Curr Med Chem 2005,12(8),887-916 10.2174/0929867053507315 15853704 Roussaki M.; Kontogiorgis C.A.; Hadjipavlou-Litina D.; Hamilakis S.; Detsi A.; A novel synthesis of 3-aryl coumarins and evaluation of their antioxidant and lipoxygenase inhibitory activity. Bioorg Med Chem Lett 2010,20(13),3889-3892 10.1016/j.bmcl.2010.05.022 20627725 Dvornikova I.A.; Buravlev E.V.; Fedorova I.V.; Shevchenko O.G.; Chukicheva I.Y.; Kutchin A.V.; Synthesis and antioxidant properties of benzimidazole derivatives with isobornylphenol fragments. Russ Chem Bull 2019,68(5),1000-1005 10.1007/s11172-019-2510-7 Anastassova N.; Argirova M.; Yancheva D.; Aluani D.; Tzankova V.; Hristova-Avakumova N.; In vitro assessment of the neuroprotective and antioxidant properties of new benzimidazole derivatives as potential drug candidates for the treatment of Parkinson’s disease. Proceedings 2019,22(1),54 10.3390/proceedings2019022054 Ayhan-Kılcıgil G.; Kus C.; Özdamar E.D.; Can-Eke B.; Iscan M.; Synthesis and antioxidant capacities of some new benzimidazole derivatives. Arch Pharm 2007,340(11),607-611 10.1002/ardp.200700088 17994646 Patagar D.N.; Batakurki S.R.; Kusanur R.; Patra S.M.; Saravanakumar S.; Ghate M.; Synthesis, antioxidant and anti-diabetic potential of novel benzimidazole substituted coumarin-3-carboxamides. J Mol Struct 2023,1274,134589 10.1016/j.molstruc.2022.134589

Rights & Permissions Print Cite

Article Metrics

46

1

Journal Information

For Authors

For Editors

For Reviewers

Explore Articles

Open Access

Open Access Articles

For Visitors

DOI https://dx.doi.org/10.2174/0109298673260463231122074253	Print ISSN 0929-8673
Publisher Name Bentham Science Publisher	Online ISSN 1875-533X

Current Medicinal Chemistry

How Important is the Metal-free Catalytic Knoevenagel Reaction in Medicinal Chemistry? An Updated Review

Abstract

Advances in Medicinal Chemistry: From Cancer to Chronic Diseases.

Approaches to the Treatment of Chronic Inflammation

Cellular and Molecular Mechanisms of Non-Infectious Inflammatory Diseases: Focus on Clinical Implications

Chalcogen-modified nucleic acid analogues

Current Medicinal Chemistry

How Important is the Metal-free Catalytic Knoevenagel Reaction in Medicinal Chemistry? An Updated Review

Abstract

Call for Papers in Thematic Issues

Advances in Medicinal Chemistry: From Cancer to Chronic Diseases.

Approaches to the Treatment of Chronic Inflammation

Cellular and Molecular Mechanisms of Non-Infectious Inflammatory Diseases: Focus on Clinical Implications

Chalcogen-modified nucleic acid analogues

Related Journals

Related Books

Related Articles