ABSTRACT
In pursuit of new antitubercular agents, we here report the antimycobacterial (H37Rv) and DNA gyrase inhibitory potential of daidzein and khellin natural products (NPs). We procured a total of 16 NPs based on their pharmacophoric similarities with known antimycobacterial compounds. The H37Rv strain of M. tuberculosis was found to be susceptible to only two out of the 16 NPs procured; specifically, daidzein and khellin each exhibited an MIC of 25 µg/mL. Moreover, daidzein and khellin inhibited the DNA gyrase enzyme with IC50 values of 0.042 and 0.822 µg/mL, respectively, compared to ciprofloxacin with an IC50 value of 0.018 µg/mL. Daidzein and khellin were found to have lower toxicity toward the vero cell line, with IC50 values of 160.81 and 300.23 µg/mL, respectively. Further, molecular docking study and MD simulation of daidzein indicated that it remained stable inside the cavity of DNA GyrB domain for 100 ns.
ABSTRACT
The condensation of phthalic anhydride afforded structurally modified isoindoline-1,3-dione derivatives with selected amino-containing compounds. The title compounds (2-30) have been characterized by thin-layer chromatography (TLC), infrared spectroscopy, 1H and 13C NMR spectroscopy, and mass spectroscopy. All of the compounds were assessed for their antimycobacterial activity toward the H37Rv strain by a dual read-out assay method. Among the synthesized compounds, compound 27 possessed a significant IC50 of 18 µM, making it the most potent compound of the series. The InhA inhibitory (IC50) activity of compound 27 was 8.65 µM in comparison to Triclosan (1.32 µM). Computational studies like density functional theory (DFT) study, molecular docking, and dynamic simulation studies illustrated the reactivity and stability of the synthesized compounds as InhA inhibitors. A quantum-mechanics-based DFT study was carried out to investigate the molecular and electronic properties, reactivities, and nature of bonding present in the synthesized compounds and theoretical vibrational (IR) and isotropic value (1H and 13C NMR) calculations.
ABSTRACT
Tuberculosis is considered as a leading health issue globally. Even though, the todays first line anti-mycobacterial treatments used in the hospital have low deaths, multidrug-resistance forms of the ailment have now spread globally and become a major issue. The wide-ranging biodiversity of medicinal plants, ocean animals have gained considerable attention for drug discovery in previous spans, and the emergence of TB drug resistance has inspired interest in judging natural products (NPs) to cure this disease. Till now, several compounds have been isolated from natural sources with anti-mycobacterial activity, few of which demonstrate significant activity and have the potential for further development. Worldwide huge natural flora and fauna are existing, this flora and fauna must be investigated for new potent lead against infectious TB. This review systematically surveys various classes of terpenoid molecules obtained from different medicinal plants, fungi, sponges, and sea plumes with anti-TB activity, which could be useful for further optimization and development in this field.
