Design, Synthesis, and Antimycobacterial Evaluation of Novel Tetrahydroisoquinoline Hydrazide Analogs. Issue 2 (16th January 2023)

• Record Type: Journal Article
• Authors: Kumar, Boddupalli Venkata Siva; Khetmalis, Yogesh Mahadu; Nandikolla, Adinarayana; Kumar, Banoth Karan; Van Calster, Kevin; Murugesan, Sankaranarayanan; Cappoen, Davie; Sekhar, Kondapalli Venkata Gowri Chandra
• Is Part Of: Chemistry & biodiversity. Volume 20:Issue 2(2023)
• Page Start: n/a
• Page End: n/a
• Publication Date: 2023-01-16
• Subjects: tetrahydroisoquinoline -- hydrazide -- Mycobacterium tuberculosis -- molecular docking; Biochemistry -- Periodicals; Molecular biology -- Periodicals; Biodiversity -- Periodicals; 572
• DOI: 10.1002/cbdv.202200939
• Languages: English
• ISSNs: 1612-1872

Abstract

Abstract: A series of novel 2‐substituted‐5, 7‐dichloro‐1, 2, 3, 4‐tetrahydroisoquinoline‐6‐carbohydrazide were designed, synthesized and structures were confirmed by analytical methods, viz ., 1 H‐NMR, 13 C‐NMR and Mass spectrometry. Synthesized derivatives were evaluated for their anti‐mycobacterial activity against Mycobacterium tuberculosis ( Mtb ) H37Ra. Among all the evaluated compounds, 10A25 containing biphenyl moiety exhibited significant inhibition with IC50 4.7 μM. 10A19, with an electron‐withdrawing Iodo group in the ortho position of the phenyl exhibited significant anti‐tubercular activity with IC50 8.8 μM. IC50 values of the remaining compounds ranged from 9.2 to 73.6 μM. Molecular docking study of the significantly active compound 10A25 was performed to determine the putative binding position of the test ligand at the active site of the selected target proteins Mycobacterium tuberculosis enoyl reductase (InhA) PDB – 4TZK and peptide deformylase PDB – 3E3U. A suitable single crystal for one of the active compounds, 10A12, was generated and analysed to further confirm the structure of the compounds. Abstract :