Design,Synthesis, and Antimycobacterial Evaluation of Novel Tetrahydroisoquinoline Hydrazide Analogs |
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Authors: | Boddupalli Venkata Siva Kumar Yogesh Mahadu Khetmalis Adinarayana Nandikolla Banoth Karan Kumar Kevin Van Calster Sankaranarayanan Murugesan Davie Cappoen Kondapalli Venkata Gowri Chandra Sekhar |
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Institution: | 1. Department of Chemistry, Birla Institute of Technology and Science, Pilani, Hyderabad Campus, Jawahar Nagar, Kapra Mandal, Hyderabad, 500078 Telangana, India;2. Medicinal Chemistry Research Laboratory, Department of Pharmacy, Birla Institute of Technology and Science, Pilani Campus, Pilani, 333031 Rajasthan, India;3. Laboratory of Microbiology, Parasitology and Hygiene (LMPH), S7, Faculty of Pharmaceutical, Biomedical and Veterinary Sciences, University of Antwerp, Wilrijk, Belgium |
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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., 1H-NMR, 13C-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. |
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Keywords: | tetrahydroisoquinoline hydrazide Mycobacterium tuberculosis molecular docking |
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