Synthesis of 6‐[4‐(4‐Propoxyphenyl)piperazin‐1‐yl]‐9H‐purine Derivatives as Antimycobacterial and Antifungal Agents: In Vitro Evaluation and In Silico Study

Abstract

A series of novel alkyl substituted purines were synthesized. 6-[4-(4-Propoxyphenyl)piperazin-1-yl]-9H-purine was used as the key starting material, which was synthesized via a multistep protocol and finally subjected for Nalkylation with various alkyl halides with an aim to get prospective antimicrobial agents. The structures of the novel compounds were established by substantiating them through spectral techniques like 1 H-NMR, 13 C-NMR, FT-IR and EI-MS. They were explored for antitubercular activity against Mycobacterium tuberculosis H37RV. Furthermore, they were checked for their antimicrobial activity concerning bacterial and fungal strains. The title compounds exhibited considerable antimicrobial activity without any significant toxicity. In silico studies depicted their good binding profile against Mycobacterium tuberculosis enoyl reductase (InhA; PDB ID: 4TZK) and Candida albicans dihydrofolate reductase (PDB ID: 1AI9). The title compounds obeyed Lipinski's parameters and have exhibited good drug-like properties.

Identification of selective mtbDHFR inhibitors by virtual screening and experimental approaches

“…

Tuberculosis (TB) is caused by mtb infection and has posed great threats to public health (W.H.O & Global tuberculosis report, 2020). Due to long treatment periods, drug resistance, and various side effects, TB's global threats have been exacerbated in recent years (Nadaf et al, 2020). Various efforts have been made in the new strategies to fight TB, but only two new drugs have recently been approved for clinic use (Furin et al, 2019;Ribeiro et al, 2020).

…”