Synthesis, Characterization, Anti-Mycobacterial Evaluation and In-Silico Molecular Docking of Novel Isoxazole Clubbed Pyrimidine Derivatives

Abstract

In the present research, we tend to ready a series of novel pyrimidine-linked isoxazole derivatives (11-20). The molecular structure and the elemental composition of these compounds were confirmed by spectroscopic studies and elemental analysis. MABA (Microplate alamar Blue Assay) assay was employed for assessing the antitubercular activity against the Mycobacterium tuberculosis H37Rv strain. Among the ten synthesized compounds, 18 and 20 showed excellent anti-tubercular activity than the reference (MIC-3.125 µg/ml) at 0.78 µg/mL. The compounds were found to possess good binding affinity than a standard against thymidylate kinase enzyme (PDB-1MRS) as evidenced by the molecular docking studies. Additionally, the bioactivity was conducted by Mol-inspiration software tool and the drug-likeness property was evaluated on Lipinski's rule of five by SCFBio online software. The lead compounds identified through these studies could be useful for the furtherance of the drug discovery process in the area of antitubercular research.

A review of recent synthetic strategies and biological activities of isoxazole

“…anti-cancer and anti-tumor [12], anti-inflammatory [13], anti-convulsant [14], anti-mycobacterial [15], antiproliferative [16], anti-viral [17], anti-oxidant [18], antitubercular [19], etc. It also has been observed that isoxazole-containing scaffold also possesses good herbicidal potency proving their utilization in the agricultural sector too [20].…”

“…Many researchers have reported the synthesis of varied derivatives consisting of isoxazole rings in their structure by various routes [8]. Isoxazole and their derivatives show different biological actions such as anti‐bacterial [9], analgesic [10], anti‐fungal [11], anti‐cancer and anti‐tumor [12], anti‐inflammatory [13], anti‐convulsant [14], anti‐mycobacterial [15], anti‐proliferative [16], anti‐viral [17], anti‐oxidant [18], anti‐tubercular [19], etc. It also has been observed that isoxazole‐containing scaffold also possesses good herbicidal potency proving their utilization in the agricultural sector too [20].…”

Isoxazole Clubbed 1-carbothioamido-4,5-dihydro-1H-pyrazoles: Design, Synthesis, Characterization and Antitubercular Evaluation

“…Among them isoxazole and dihydropyrazole were of special interest to medicinal chemists, owing to their useful biological actions. Both these rings are not only the part of many drug molecules but their derivatives were reported with significant activities including antitubercular [2][3][4][5][6][7][8][9], antioxidant [10][11], anticancer [12,13], antibacterial [14,15], antifungal [16,17]. Hence, combining these two rings into a single molecule has a greater propensity of improving the activity of new analogues.…”