Synthesis, Anticancer Evaluation and DNA‐Binding Spectroscopic Insights of Quinoline‐Based 1,3,4‐Oxadiazole‐1,2,3‐triazole Conjugates

Abstract

The present work involves a pharmacophore hybridization strategy to combine key biologically active scaffolds. The study led to the synthesis of quinoline based oxadiazole‐triazole conjugates with favorable physicochemical properties as anti‐cancer agents. Among the synthesized compounds 8(a–p), in vitro screening against a panel of four cancer cell lines identified compound 8k, with o‐chloro substitution on the phenyl ring, as potent against human lung carcinoma (A‐549) cells (IC50 =5.6 μM), while showing no significant cytotoxicity upto 200 μM concentration in normal cells. Compound 8 k with o‐chloro substitution induced nuclear morphological changes in A‐549 cells as visualized by DAPI (4,6‐diamidino‐2‐phenylindole) and was shown to bind firmly with A−T rich region in DNA. Changes in DNA topology studied through gel electrophoresis and groove mode of binding to ct‐DNA through multi‐spectroscopic techniques were observed, further validated by molecular docking studies. Overall, the study illustrates successful hybridization strategy leading to compound 8 k as promising anticancer agent for further structural optimization and biological evaluation.

1,2,3-Triazole-Containing Compounds as Anti–Lung Cancer Agents: Current Developments, Mechanisms of Action, and Structure–Activity Relationship

“…Some 1,2,3triazole-containing 2-chloroquinoline derivatives, such as compound 29 (IC 50 : 9.8 μm against A549 cells, MTT assay; 9.7 μm for doxorubicin), also display certain antiproliferative activity against lung cancer cells, but most of them are less potent than the references (Praveena et al, 2016;Dasari et al, 2019). Further modifications implies that incorporation of azole between 1,2,3-triazole and quinoline moieties is also allowed, and 1,2,3-triazole-tethered 1,3,4-oxadiazole-quinoline compound 30 (IC 50 : 5.6 μm, MTT assay) is comparable to doxorubicin (IC 50 : 1.83 μm) against A549 cells (Rachakonda et al, 2017;Shamsi et al, 2019).…”

Synthesis and antimicrobial activity of new 1,2,4‐triazole, 1,3,4‐oxadiazole, 1,3,4‐thiadiazole, thiopyrane, thiazolidinone, and azepine derivatives

“…All compounds were tested in vitro to microbial activity (bacteria and fungi) and all the results were offered in Tables 1 and 2 μmol cm −3 of 14a-c (1-5), 13 (2-6), 12a-c (4-8), and 11a-c (6-10) when compared with the positive control, nystatin (MIC 2-5 μmol mL −1 ). Some of the compounds showed moderate antifungal activity when compared with nystatin (MIC 2-5 μmol mL −1 ): 10a-c (8-12), 9a-c (10-15), 8a-c (13)(14)(15)(16)(17), and 5a-c (15)(16)(17)(18)(19). The tested fungi were Candida albicans, Curvularia lunata, Alternaria alternata, and Aspergillus niger.…”

“…[15] Moreover, the interaction of 1,3,4-oxadiazole or 1,3,4-thiadiazole derivatives with CT-DNA was investigated by different spectroscopic methods, [16,17] hence can benefit in understanding the binding mechanism of heterocyclic molecules and the design of new effective molecules. Also, the interaction of DNA with 1,3,4-oxadiazoles or 1,3,4-thiadiazoles lead to the formation of antiproliferative cells, anticancer and antitumor agents through many scientific studies, [18][19][20] thus these compounds have the ability to the binding to DNA which makes researchers use these compounds to develop many drugs in the future.…”

Recent Advances in the Synthesis and Biological Activity of 8-Hydroxyquinolines

“…In addition, Shamsi and coworkers prepared 16 quinoline-based 1,3,4-oxadiazole-triazole derivatives ( Scheme 14 ) based on the hybrid strategy of nitrogen-containing heterocyclic scaffolds [ 36 ]. These compounds were considered to be high-impact motifs with a wide range of biological activities [ 37 , 38 ].…”