Synthesis of indole-functionalized isoniazid conjugates with potent antimycobacterial and antioxidant efficacy.
Renu GavadiaJyoti RasganiaNeetu SahuMandira Varma-BasilVarsha ChauhanSanjay KumarSatbir MorDevender SinghKomal JakharPublished in: Future medicinal chemistry (2024)
Aim: Developing potent medicinal alternates for tuberculosis (TB) is highly desirable due to the advent of drug-resistant lethal TB strains. Methods & results: Novel indole-isoniazid integrates have been synthesized with promising antimycobacterial action against the H37Rv strain, and the nitro analogs 4e and 4j show the highest efficacy with a minimum inhibitory concentration of 1.25 μg/ml. The molecular docking studies against InhA support the experimental findings. Indole conjugates display remarkable radical quenching efficiency, and compounds 4e and 4j demonstrate maximum IC 50 values of 50.19 and 52.45 μg/ml, respectively. Pharmacokinetic analysis anticipated appreciable druggability for the title compounds. Conclusion: The notable bioaction of the indole-isoniazid templates projects them as potential lead in developing anti-TB medications with synergetic antioxidant action.
Keyphrases
- mycobacterium tuberculosis
- molecular docking
- drug resistant
- anti inflammatory
- pulmonary tuberculosis
- multidrug resistant
- acinetobacter baumannii
- molecular dynamics simulations
- oxidative stress
- escherichia coli
- quality improvement
- risk assessment
- drug delivery
- climate change
- cystic fibrosis
- adverse drug
- drug discovery