Ultrasound-assisted ionic liquid-mediated green method for synthesis of 1,3-diphenylpyrazole-based spirooxindolopyrrolizidines, their anti-tubercular activity, molecular docking study and ADME predictions

• Published in: New journal of chemistry Vol. 48; no. 22; pp. 997 - 998
• Main Authors: Baddepuri, Sravanthi, Gamidi, Rama Krishna, Kumari, Jyothi, Sriram, Dharmarajan, Basavoju, Srinivas
• Format: Journal Article
• Language: English
• Published: CAMBRIDGE Royal Soc Chemistry 2024; Royal Society of Chemistry
• Subjects: Chemistry; Chemistry, Multidisciplinary; Ionic liquids; Molecular docking; Physical Sciences; Reductases; Science & Technology; Single crystals; Spectral methods; Synthesis; Tuberculosis; ANTIBACTERIAL; CYCLOADDITION; DESIGN; ANALOGS; DERIVATIVES
• ISSN: 1144-0546; 1369-9261
• DOI: 10.1039/d4nj00563e

The aim of the study is to develop the synthesis of a novel series of potent anti-tubercular (anti-TB) activity of 1,3-diphenylpyrazole-based spirooxindolopyrrolizidine derivatives via an efficient green approach achieved by using an ionic liquid ([Bmim]BF 4 ) under ultrasonication. The title compounds 4a - 4ad with a general molecular formula C a H b X (0-2) N c O d (X = F/Cl/Br) were produced with high yields in shorter reaction time and well characterized by using spectral techniques; and finally single crystal X-ray diffraction method ( 4b ). The newly synthesized compounds were evaluated for their in vitro anti-TB activity against Mycobacterium tuberculosis H37Rv strain. Among all, six compounds 4e (C 36 H 29 N 5 O 4 ), 4g (C 34 H 28 N 4 O 3 ), 4q (C 36 H 28 F 2 N 4 O 2 ), 4r (C 36 H 28 ClFN 4 O 2 ), 4y (C 36 H 29 BrN 4 O 2 ) and 4z (C 36 H 28 BrFN 4 O 2 ) exhibited significant anti-TB activity with MIC value 6.25 μg mL −1 , when compared to the standard drug ethambutol (MIC:1.56 μg mL −1 ). In silico molecular docking studies were performed against M. tuberculosis enoyl-acyl carrier protein reductase inhibitor. The compounds 4o , 4p , 4y and 4aa were exhibited least binding energies −12.58, −12.61, −12.58 and −12.57 kcal mol −1 , respectively. These results reveal that the produced compounds might be used for the future generation of novel anti-TB drugs. The study aims to develop and synthesis of a novel series of 1,3-diphenylpyrazole-based spirooxindolopyrrolizidine derivatives as potent anti-TB agents via an efficient green approach by using an ionic liquid ([Bmim]BF 4 ) under ultrasonication.