Thiadiazole-thiazole derivatives as potent anti-tubercular agents: Synthesis, biological evaluation, and In silico docking studies
The present study focuses on research findings related to the development and assessment of thiadiazole-linked thiazole derivatives as promising anti-tubercular agents. We present the synthesis data of eleven new compounds (4a-4k) and confirm their structures using spectroscopic techniques. Subseque...
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| Language: | English |
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Elsevier
2024-12-01
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| Series: | European Journal of Medicinal Chemistry Reports |
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| Online Access: | http://www.sciencedirect.com/science/article/pii/S2772417424000554 |
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| author | Samin A. Shaikh Shivaji R. Labhade Raju R. Kale Prajakta Y. Pachorkar Rohan J. Meshram Kamlesh S. Jain Hrishikesh S. Labhade Dipak D. Bhanushali Rahul A. More Charushila K. Nerkar Santosh S. Chobe Aniket N. Marathe Satish N. Wakchaure Deepak R. Boraste |
| author_facet | Samin A. Shaikh Shivaji R. Labhade Raju R. Kale Prajakta Y. Pachorkar Rohan J. Meshram Kamlesh S. Jain Hrishikesh S. Labhade Dipak D. Bhanushali Rahul A. More Charushila K. Nerkar Santosh S. Chobe Aniket N. Marathe Satish N. Wakchaure Deepak R. Boraste |
| author_sort | Samin A. Shaikh |
| collection | DOAJ |
| description | The present study focuses on research findings related to the development and assessment of thiadiazole-linked thiazole derivatives as promising anti-tubercular agents. We present the synthesis data of eleven new compounds (4a-4k) and confirm their structures using spectroscopic techniques. Subsequently, the compounds were screened for their anti-tuberculosis activities against M. tuberculosis H37Ra. The results demonstrated that compounds 3 and 4b exhibited minimum inhibitory concentration (MIC) of 3.90 μg/mL and 7.81 μg/mL, respectively. In-vitro, studies for few compounds exhibited high antioxidant activity against DPPH and OH radical scavengers along with minimal to no cytotoxicity against RBCs which is a promising result. Investigation of molecular docked conformations revealed different molecular interactions such as hydrogen bonds, halogen bonds, and interactions involving Pi electron cloud. The study sheds light on conserved interactions with residues like Met131, Val163, His90 and Gln161 from the tubercular MCAT enzyme. Interestingly, the synthetic chemistry reveals that the employment of tetra-n-butylammonium bromide (TBAB) plays a crucial role for N-butylation and it also expedites the reaction in tetrahydrofuran solvent. |
| format | Article |
| id | doaj-art-2b41aece8a7c44a79eb3205b51c8e6d9 |
| institution | Kabale University |
| issn | 2772-4174 |
| language | English |
| publishDate | 2024-12-01 |
| publisher | Elsevier |
| record_format | Article |
| series | European Journal of Medicinal Chemistry Reports |
| spelling | doaj-art-2b41aece8a7c44a79eb3205b51c8e6d92024-12-05T05:21:48ZengElsevierEuropean Journal of Medicinal Chemistry Reports2772-41742024-12-0112100183Thiadiazole-thiazole derivatives as potent anti-tubercular agents: Synthesis, biological evaluation, and In silico docking studiesSamin A. Shaikh0Shivaji R. Labhade1Raju R. Kale2Prajakta Y. Pachorkar3Rohan J. Meshram4Kamlesh S. Jain5Hrishikesh S. Labhade6Dipak D. Bhanushali7Rahul A. More8Charushila K. Nerkar9Santosh S. Chobe10Aniket N. Marathe11Satish N. Wakchaure12Deepak R. Boraste13Department of Chemistry, KTHM College, Gangapur Road, Nashik, Maharashtra, India; Department of Chemistry, Kr. V. N. Naik Shikshan Prasarak Sanstha's Arts, Commerce and Science College, Canada Corner, Nashik, Maharashtra, India; Corresponding author. Department of Chemistry, KTHM College, Gangapur Road, Nashik, Maharashtra, India.Department of Chemistry, KTHM College, Gangapur Road, Nashik, Maharashtra, IndiaDepartment of Chemistry, KTHM College, Gangapur Road, Nashik, Maharashtra, IndiaDepartment of Microbiology, KTHM College, Gangapur Road, Nashik, Maharashtra, IndiaBioinformatics Centre, Savitribai Phule Pune University, Pune, Maharashtra, IndiaDepartment of Chemistry, Kr. V. N. Naik Shikshan Prasarak Sanstha's Arts, Commerce and Science College, Canada Corner, Nashik, Maharashtra, IndiaDepartment of Chemistry, KTHM College, Gangapur Road, Nashik, Maharashtra, IndiaDepartment of Chemistry, Kr. V. N. Naik Shikshan Prasarak Sanstha's Arts, Commerce and Science College, Canada Corner, Nashik, Maharashtra, IndiaDepartment of Microbiology, Dayanand Science College, Latur, Maharashtra, IndiaDepartment of Chemistry, M.G. V's Loknete Vyankatrao Hiray, Arts, Science and Commerce College, Panchavati, Nashik, Maharashtra, IndiaDepartment of Chemistry, M.G. V's Loknete Vyankatrao Hiray, Arts, Science and Commerce College, Panchavati, Nashik, Maharashtra, IndiaBioinformatics Centre, Savitribai Phule Pune University, Pune, Maharashtra, IndiaDepartment of Synthetic R & D, Delta Finochem Private Limited, Gat No. 350, Village Wadivarhe, Tal-Igatpuri, Nashik, Maharashtra, IndiaG. E. Society's, R.N.C Arts, J.D.B Commerce, and N.S.C. Science College, Nashik Road, Nashik, 422101, Maharashtra, IndiaThe present study focuses on research findings related to the development and assessment of thiadiazole-linked thiazole derivatives as promising anti-tubercular agents. We present the synthesis data of eleven new compounds (4a-4k) and confirm their structures using spectroscopic techniques. Subsequently, the compounds were screened for their anti-tuberculosis activities against M. tuberculosis H37Ra. The results demonstrated that compounds 3 and 4b exhibited minimum inhibitory concentration (MIC) of 3.90 μg/mL and 7.81 μg/mL, respectively. In-vitro, studies for few compounds exhibited high antioxidant activity against DPPH and OH radical scavengers along with minimal to no cytotoxicity against RBCs which is a promising result. Investigation of molecular docked conformations revealed different molecular interactions such as hydrogen bonds, halogen bonds, and interactions involving Pi electron cloud. The study sheds light on conserved interactions with residues like Met131, Val163, His90 and Gln161 from the tubercular MCAT enzyme. Interestingly, the synthetic chemistry reveals that the employment of tetra-n-butylammonium bromide (TBAB) plays a crucial role for N-butylation and it also expedites the reaction in tetrahydrofuran solvent.http://www.sciencedirect.com/science/article/pii/S2772417424000554Anti-tuberculosisThiazoleTetra-n-butylammonium bromideThiadiazole |
| spellingShingle | Samin A. Shaikh Shivaji R. Labhade Raju R. Kale Prajakta Y. Pachorkar Rohan J. Meshram Kamlesh S. Jain Hrishikesh S. Labhade Dipak D. Bhanushali Rahul A. More Charushila K. Nerkar Santosh S. Chobe Aniket N. Marathe Satish N. Wakchaure Deepak R. Boraste Thiadiazole-thiazole derivatives as potent anti-tubercular agents: Synthesis, biological evaluation, and In silico docking studies European Journal of Medicinal Chemistry Reports Anti-tuberculosis Thiazole Tetra-n-butylammonium bromide Thiadiazole |
| title | Thiadiazole-thiazole derivatives as potent anti-tubercular agents: Synthesis, biological evaluation, and In silico docking studies |
| title_full | Thiadiazole-thiazole derivatives as potent anti-tubercular agents: Synthesis, biological evaluation, and In silico docking studies |
| title_fullStr | Thiadiazole-thiazole derivatives as potent anti-tubercular agents: Synthesis, biological evaluation, and In silico docking studies |
| title_full_unstemmed | Thiadiazole-thiazole derivatives as potent anti-tubercular agents: Synthesis, biological evaluation, and In silico docking studies |
| title_short | Thiadiazole-thiazole derivatives as potent anti-tubercular agents: Synthesis, biological evaluation, and In silico docking studies |
| title_sort | thiadiazole thiazole derivatives as potent anti tubercular agents synthesis biological evaluation and in silico docking studies |
| topic | Anti-tuberculosis Thiazole Tetra-n-butylammonium bromide Thiadiazole |
| url | http://www.sciencedirect.com/science/article/pii/S2772417424000554 |
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