Antimicrobial and antiproliferative activities of novel synthesized 6‐(quinolin‐2‐ylthio) pyridine derivatives with molecular docking study as multi‐targeted JAK2/STAT3 inhibitors. (26th September 2020)

• Record Type: Journal Article
• Authors: Nafie, Mohamed S.; Mahgoub, Sebaey; Amer, Atef M.
• Is Part Of: Chemical biology & drug design. Volume 97:Number 3(2021)
• Page Start: 553
• Page End: 564
• Publication Date: 2020-09-26
• Subjects: 6‐(quinolin‐2‐ylthio) pyridine -- antimicrobial -- antiproliferative -- Jak2/STAT3; Drugs -- Design -- Periodicals; Pharmaceutical chemistry -- Periodicals; Biochemistry -- Periodicals; 615.19005
• DOI: 10.1111/cbdd.13791
• Languages: English
• ISSNs: 1747-0277

Abstract

Abstract: Quinoline derivatives are attracting considerable interest due to their biological importance. In this paper, several 2‐amino‐4‐aryl‐6‐(quinolin‐2‐ylthio)pyridine‐3, 5‐dicarbonitrile derivatives are synthesized by adopting a one‐pot reaction of quinoline‐2‐thione, aromatic aldehydes, and malononitrile in the presence of sodium hydroxide in absolute ethanol. The structures of these newly synthesized compounds were determined using different spectroscopic techniques, including elemental analyses, IR, 1 H NMR, and MS. The synthesized derivatives were screened for their antimicrobial and cytotoxic activities. Compounds 4a, 4b, 4d, and 4e exhibited promising antimicrobial activity compared to antibacterial and antifungal standard drugs. Additionally, 4f, 4d, and 4g showed potent cytotoxic activity against both MCF‐7 and A549 cells with IC50 values (6.39–9.3 μM). Our molecular docking results of compound 4f prove good binding affinity toward the three tested proteins as Jak2/STATA3 inhibition and are in accordance with the RT‐PCR mRNA expressions of the compound against MCF‐7 cells which downregulated the Jak2 and STAT3 genes, and this may be the proposed mode of action for anti‐breast cancer activity. Abstract : Compound 4f exhibited potent cytotoxic activity against MCF‐7 and A549 cell lines with IC50 = 6.39 and 6.9 µM, respectively with elucidated JAK2/STAT3 inhibition using gene expression and in silico approaches.