Title:New Quinoline Based Sulfonamide Derivatives: Cytotoxic and Apoptotic Activity Evaluation Against Pancreatic Cancer Cells
Volume: 18
Issue: 8
Author(s): Leyla Yurttaş*Gülşen A. Çiftçi
Affiliation:
- Department of Pharmaceutical Chemistry, Faculty of Pharmacy, Anadolu University, 26470 Eskisehir,Turkey
Keywords:
Quinoline, sulphonamide, pancreas cancer, cytotoxicity, apoptosis, pancreatic cancer cells, CAPAN-1.
Abstract: Background: Quinoline is a privileged scaffold especially known with antimalarial and antibacterial
drugs before, presently followed anticancer efficiency with a new group of protein kinase inhibitors.
Objective: In this work, combining quinoline ring, hydrazone and sulphonamide groups, we have synthesized
N'-arylidene-2-[4-(quinolin-8-ylsulfonyl)piperazin-1-yl]acetohydrazide derivatives (3a-o) and evaluated their in
vitro anticancer activity against cancerous cell lines PANC-1, CAPAN-1, and healthy cell line hTERT-HPNE.
Method: Fifteen compounds were synthesized a simple, well-known three-step synthetic procedure starting
from 8-quinolinesulfonylchloride. Cytotoxicity studies were performed according to the conventional MTT
method. As a second stage, flow cytometric analysis was done to the nine most cytotoxic compounds for determining
the mechanism of action which could be apoptosis and/or necrosis.
Results/Conclusion: According to anticancer activity evaluation, compound 3b bearing 4-methyl phenyl moiety
exhibited significant cytotoxicity which has an IC50 value nearly four-fold lower than cisplatin displayed,
whereas compound 3f bearing 4-trifluoromethyl phenyl moiety showed two-fold potency of the standard drug
against PANC-1 cell line. Compounds 3h, 3k and 3n against CAPAN-1 also showed significant cytotoxicity,
selectively. The most active compounds 3b, 3c, 3d, 3f, 3g, 3h, 3k and 3n against PANC-1 and compounds 3f,
3g, 3h, 3k and 3n against CAPAN-1 were selected to be studied in flow cytometry. Compound 3b induced
apoptosis of PANC-1 cells with a percentage of 16.0%, whereas compound 3h induced apoptosis of CAPAN-1
cells with a value of 20.6%.
