Structure-based design,synthesis and biological evaluation of a newer series of pyrazolo[1,5-a]pyrimidine analogues as potential anti-tubercular agents |
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| Affiliation: | 1. Department of Pharmaceutical Chemistry, L. M. College of Pharmacy, Navrangpura, Ahmedabad, 380009 Gujarat, India;2. Department of Pharmacy, Dharmsinh Desai University, Nadiad, 387001 Gujarat, India;3. Division of Biological and Life Sciences, Ahmedabad University, Ahmedabad, 380009 Gujarat, India;4. Department of Pharmaceutical Chemistry, L. J. Institute of Pharmacy, Ahmedabad, 382210 Gujarat, India;1. Deparment of Applied Organic Chemistry, National Research Centre, 12622 Dokki, Egypt;2. Department of Photochemistry, National Research Centre, 12622 Dokki, Egypt;3. Department of Green Chemistry, National Research Centre, 12622 Dokki, Egypt;4. Department of Medicinal Chemistry, Faculty of Pharmacy, Mansoura University, 35516 Mansoura, Egypt;5. Department of Pharmaceutical Organic Chemistry, Faculty of Pharmacy, Mansoura University, 35516 Mansoura, Egypt;6. Department of Pharmacology and Toxicology, Faculty of Pharmacy, Mansoura University, 35516 Mansoura, Egypt;7. National Cancer Institute, Chemotherapeutic Agents Repository, Fisher BioServices, Germantown, MD 20874, USA;1. Postovsky Institute of Organic Synthesis, Ural Branch of the Russian Academy of Sciences, S. Kovalevskoy Str, 22, Ekaterinburg 620990, Russia;2. Ural Federal University, Mira St. 19, Ekaterinburg 620002, Russia;3. Ural Research Institute for Dermatology, Venereology and Immunopathology, Scherbakova St., 8, Ekaterinburg 620076, Russia;4. Ural Research Institute for Phthisiopulmonology, 22 Parts’ezda St, 50, Ekaterinburg 620039, Russia;1. Department of Pharmaceutical Chemistry, Faculty of Pharmacy (girls), Al-Azhar University, Nasr City, Cairo, Egypt;2. Department of Organic Chemistry, Faculty of Science, Ain Shams University, Abbassia, 11566 Cairo, Egypt;1. Faculty of Chemistry, VNU University of Science, 19 Le Thanh Tong, Ha Noi, Viet Nam;2. Institute of Technique in Chemistry, Biology and Security Documents (Ministry of Public Security), Cau Giay, Ha Noi, Viet Nam;3. Faculty of Chemical Technology, Viet Tri University of Industry, Tien Kien, Lam Thao, Phu Tho, Viet Nam;4. Institute for Chemistry and Materials, Military Institute of Science and Technology (Ministry of Military), Cau Giay, Ha Noi, Viet Nam;5. Faculty of Chemistry, Thai Nguyen University of Education, 20 Luong Ngoc Quyen, Thai Nguyen, Viet Nam;6. Thai Nguyen College of Education, Quang Trung, Thinh Dan, Thai Nguyen, Viet Nam |
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| Abstract: | In-depth study of structure-based drug designing can provide vital leads for the development of novel, clinically active molecules. In this present study, twenty six novel pyrazolo[1,5-a]pyrimidine analogues (6a-6z) were designed using molecular docking studies. The designed molecules were synthesized in good yields. Structural elucidation of the synthesized molecules was carried out using IR, MS, 1H NMR and 13C NMR spectroscopy. All the synthesized compounds were evaluated for their in-vitro anti-tubercular activity against H37Rv strain by Alamar Blue assay method. Most of the synthesized compounds displayed potent anti-tubercular activities. Amongst all the tested compounds 6p, 6g, 6n and 6h exhibited promising anti-tubercular activity. Further, these potent compounds were gauged for MDR-TB, XDR-TB and cytotoxic study. None of these compounds exhibited potent cytotoxicity. Stability of protein ligand complex was further evaluated by molecular dynamics simulation for 10 ns. All these results indicate that the synthesized compounds could be potential leads for further development of new potent anti-tubercular agents. |
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| Keywords: | Molecular docking Molecular dynamics |
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