Cytotoxic, DNA Cleavage and Pharmacokinetic Parameter Study of Substituted Novel Furan C-2 Quinoline Coupled 1, 2, 4-Triazole and Its Analogs

Abstract

Background:Furan, quinoline and triazoles are known for their wide spectrum biologically active molecules. A series of novel furan C-2 quinoline and 1, 2, 4-triazole (FQT) coupled hybrids were designed and synthesized to evaluate for their DNA cleavage and cytotoxic studies.Objectives:In this work we describe the synthesis and biological evaluation of furan C-2 quinoline coupled triazoles exposed for cytotoxic and DNA cleavage study.Methods:The electrophoretic DNA cleavage studies on λ-DNA (Eco-RI/Hinda-III double digest) using agarose gelelectrophoresis and the cytotoxic activity were carried out by MTT assay method.Results:The results revealed that, the molecules 7(a-o) did cleave the DNA completely with no trace of fragments at 100 µg concentration, on the other hand, cytotoxic assay was achieved by two different human cancer cell lines (melanoma cell line-A375 and breast cancer cell line MDA-MB 231). Among the synthesized compounds 7a, 7b, 7c and 7k exhibited potent cytotoxic activity with IC50 values ranging from 2.9, 4.0, 7.8 and 5.1 µg/ml against A375 and 6.2, 9.5, 11.3 and 7.3 µg/ml against, MDA-MB 231, respectively.Conclusion:In synthesized compounds 7(a-o) exhibited complete DNA cleavage at 100 µg/ml and the compounds 7a, 7b, 7c and 7k showed very less cytotoxic in nature. The structure activity relationship revealed that, the presence of halogen group/atoms at para position of phenyl ring remarkably enhanced the DNA cleavage and cytotoxic activities among the synthesized compounds.

Cytotoxic effect of a 3-(4-chlorophenyl)-5-(4-methoxybenzyl)-4H-1,2,4-triazole derivative compound in human melanoma cells

“…One of the group of chemicals are 1,2,4-triazole compounds and drug development studies have been focused on the design and synthesize these compounds due to their clinical importance [15; 24-26]. There are some studies investigating the cytotoxic effects of various compounds containing 1,2,4-triazole on leukemia, lung, prostate, breast, ovary, and colon and melanoma cancer cells [24][25][26][27]. Bekircan et al [14] reported that asymmetric 3,5-diaryl-4H-1,2,4-triazole derivatives have cytotoxic effects on various melanoma cell lines and IC 50 values varied in the range of 6.18-19.6 μM.…”

“…Georgiyants et al [24] also demonstrated that the new 1,2,4-triazole (4H) derivatives exhibited cytotoxic effects on melanoma cells at different range. Novel furan C-2 quinoline coupled 1,2,4-triazole analogs were also shown to have a cytotoxic effect on melanoma (A375) cells and the IC 50 values changed between 2.9 and 207.1 µg/mL [26]. 5-mercapto-1,2,4-triazole derivatives exhibited moderate cytotoxic effect on melanoma (A375 and B164A5) cells [25].…”

Synthesis, biological screening, in silico study and fingerprint applications of novel 1, 2, 4‐triazole derivatives

“…Structure of synthesized molecules was drawn by using Chem Draw . Energy minimization protocol and macro molecular force field was used to perform Ligand optimization . Different ligand conformations were produced on the basis of their dihedral energy, bond energy, initial potential energy, CHARM energy values.…”

“…Cytotoxic activity of all compounds was studied against A375, MDA-MB 231 cancer cells and HEK293 normal cells using MTT assay. [39,40] Cell lines were obtained from National Centre For Cell Science (NCCS Pune, India), cultured in Dulbecco's modified Eagle's medium (DMEM) supplemented with 10% heat-inactivated fetal bovine serum, 2 mmoL/L glutamine, 1% antibiotics solution (100 U/mL penicillin G and 100 mg/mL streptomycin). Cells were grown in 25 cm 2 tissue culture flasks and maintained at 37 C in a humidified incubator with 5% CO 2 .…”

Navigating the Synthesis of Quinoline Hybrid Molecules as Promising Anticancer Agents

“…SAR study predicted that halogens at para position of the aldehyde moiety have particular emphasis on the anticancer activity (Scheme 13). [70] Guided by the precedents established in the literature about the therapeutic potentials of hybrid scaffolds, the group of Eman E. Nasr approached the design and synthesis of new quinoline-triazole-chromene derivatives by the fusion of quinoline, triazole and chromene as pharmacophoric units. The desired hybrid analogs were achieved by [3 + 2] cycloaddition, Knoevengel condensation followed by Michael addition reaction.…”