Design, synthesis and docking studies of novel thiazole derivatives incorporating pyridine moiety and assessment as antimicrobial agents

Abstract

A novel series of substituted 4,6-dimethyl-2-oxo-1-(thiazol-2-ylamino)-1,2-dihydropyridine-3-carbonitrile derivatives 6, 9, 13, 15, and 17 was synthesized in a good to excellent yield from the reaction of 1-(3-cyano-4,6-dimethyl-2-oxopyridin-1(2H)-yl)thiourea with 2-oxo-N'-arylpropanehydrazonoyl chloride, chloroacetone, α-bromoketones, ethyl chloroacetate, and 2,3-dichloroquinoxaline, respectively. The potential DNA gyrase inhibitory activity was examined using in silico molecular docking simulation. The novel thiazoles exhibit dock score values between − 6.4 and − 9.2 kcal/mol and they were screened for their antimicrobial activities. Compound 13a shown good antibacterial activities with MIC ranged from 93.7–46.9 μg/mL, in addition, it shown good antifungal activities with MIC ranged from 7.8 and 5.8 μg/mL.

The Expanding Role of Pyridine and Dihydropyridine Scaffolds in Drug Design

“…Because of the phenyl ring's size and inductive impact, the presence of an electron-withdrawing group might be responsible for excellent activity. 189 Pyridine rings containing 1,3,4-oxadiazole derivatives were explored by Lak et al 190 All synthesized compounds were evaluated for their antibacterial activity against 23). The key point in this study was the single-step synthesis of oxadiazole-pyridine derivative.…”

Synthesis, and docking studies of novel heterocycles incorporating the indazolylthiazole moiety as antimicrobial and anticancer agents

“…The broad-spectrum antibacterial activity of compound 3 may be attributed to the incorporated thiazolopyridine moiety, which is accordant to 56 . Khidre and Radini, reported the broad-spectrum potency of the thiazolopyridine nucleus and its derivative against many human pathogens, hypothesized that, the possible mechanisms of the thiazolopyridine nucleus antimicrobial activity is through targeting and inactivating vital microbial enzymes such as DNA gyrase 57 .…”

Synthesis, computer‐aided ADMET prediction, and molecular docking of novel 3,5,6‐trichloropyridin‐2‐yl derivatives as potential antimicrobial agents

“…2.2 | Synthesis of 3,5,6-trichloropyridin-2-yl derivatives (1)(2)(3)(4)(5)(6)(7)(8) 3,5,6-Trichloropyridin-2-yl derivatives were synthesized according to the method of Shet and Shelar [11] with some modifications. Sodium metal was added to a DMSO solution containing 3,5,6-trichloropyridin-2-ol and refluxed for 20 min to form sodium 3,5,6-trichloropyridin-2-olate (Scheme 1).…”

“…[1,2] Pyridine compounds are among the most important class, which have a wide range of biological profiles, including antibacterial, antiviral, antioxidant, antidiabetic, anticancer, and anti-inflammatory properties. [3][4][5][6] In addition, compounds containing the 3,5,6-trichloropyridine scaffold such as 3,5,6-trichloro-2-pyridinol and 2-methoxy 3,5,6-trichloropyridine derivatives play an essential role in the drug research as a result of strong biological activity including antimicrobial and pesticidal activities. [7,8] Among these derivatives, 3,5,6-trichloro-2-pyridinol is one of the most promising compounds because it is a metabolite of chlorpyrifos, an organophosphorus insecticide.…”