Synthesis, evaluation, molecular docking, and molecular dynamics studies of novel N‐(4‐[pyridin‐2‐yloxy]benzyl)arylamine derivatives as potential antitubercular agents

Abstract

A new series of novel triclosan (2,4,4 0 -trichloro-2 0 -hydroxydiphenylether) analogues were designed, synthesized, and screened for their in vitro antimycobacterial and antibacterial activities. Most of the compounds showed significant activity against Mycobacterium tuberculosis H37Rv strain with minimum inhibitory concentration (MIC) values in 20-40 μM range in GAST/Fe medium when compared with triclosan (43 μM) in the first week of assay, and after additional incubation, seven compounds, that is, 2a, 2c, 2g, 2h, 2i, 2j, and 2m, exhibited MIC values at the concentration of 20-40 μM. The compounds also showed more significant activity against Bacillus subtilis and Staphylococcus aureus. The synthesized compounds showed druggable properties, and the predicted ADME (absorption, distribution, metabolism, and excretion)properties were within the acceptable limits. The in silico studies predicted better interactions of compounds with target protein residues and a higher dock score in comparison with triclosan. Molecular dynamics simulation study of the most active compound 2i was performed in order to further explore the stability of the proteinligand complex and the protein-ligand interaction in detail. K E Y W O R D Smolecular dynamics, mycobacterial enoyl-reductase (InhA), pyridine, triclosan

Endophytic Bacillus spp. from medicinal plants inhibit mycelial growth of Sclerotinia sclerotiorum and promote plant growth

“…The chain was shown to engage the substrate binding loop, matching the arrangement seen by Rozwarski et al with their C16 substrate mimic [28,29]. In the quest for new inhibitors, other research groups have since explored different modifications of the core TCS structure [23,25,26,28,[30][31][32][33][34][35][36][37][38][39][40][41][42][43][44][45][46][47]. Rodriguez et al explored combining two TCS molecules and synthesised a novel macrocyclic InhA inhibitor [48].…”

Synthesis, In Vivo Anticonvulsant Activity Evaluation and In Silico Studies of Some Quinazolin-4(3H)-One Derivatives

“…Molecular dynamics simulation techniques recently became an important tool in developing new bioactive agents, as a complementary tool to the molecular docking techniques [72][73][74][75].…”

“…The literature described the effect of methaqualone and its quinazolin-4-one analogues as positive allosteric modulators of the GABA A receptor [7,74,76]. Consequently, this study focused on carbonic anhydrase II as the second potential target for our compounds.…”

Conventional and microwave‐assisted organic synthesis of novel antimycobacterial agents bearing furan and pyridine hybrids

“…Furan is an antitubercular compound with one oxygen atom in its moiety (Chiarelli et al, 2019; Kantevari et al, 2011; Yan et al, 2020; Yempala et al, 2014). By combining three hybrid motifs, we may expect the enhancement of the activity of synthesized compounds (5a‐o) (Desai et al, 2020; Desai, Mehta, et al, 2021; Desai, Vaghani, et al, 2021; Eryılmaz et al, 2020; Mejía‐Gutiérrez et al, 2020; Tan et al, 2020; Verma et al, 2020). The antitubercular activity of all newly synthesized compounds was assessed, and the structures of novel compounds were assigned using various spectroscopic techniques.…”