In silico docking studies and synthesis of new phosphoramidate derivatives of 6-fluoro-3-(piperidin-4-yl)benzo[d]isoxazole as potential antimicrobial agents. (2nd September 2020)

• Record Type: Journal Article
• Authors: Sivala, Munichandra Reddy; Chintha, Venkataramaiah; Potla, Krishna Murthy; Chinnam, Sampath; Chamarthi, Naga Raju
• Is Part Of: Journal of receptor and signal transduction research. Volume 40:Number 5(2020)
• Page Start: 486
• Page End: 492
• Publication Date: 2020-09-02
• Subjects: Phosphoramidates -- benzisoxazole -- anti-bacterial activity -- anti-fungal activity -- molecular docking; Cell receptors -- Periodicals; Cellular signal transduction -- Periodicals; 571.6
• DOI: 10.1080/10799893.2020.1752719
• Languages: English
• ISSNs: 1079-9893

Abstract

Abstract: A new class of phosphoramidate derivatives of 6-fluoro-3-(piperidin-4-yl)benzo[ d ]isoxazole were synthesized in good to excellent yields (78–96%) by an in situ, three-step process. All the synthesized molecules were evaluated for anti-bacterial and anti-fungal activities using in vitro and in silico methods. The results revealed that the compounds 4b, 4d, 4h, 4i, and 4j exhibited the most promising anti-bacterial activity against S. aureus, B. subtilis, K. pneumoniae, S. typhi and P. mirabilis and anti-fungal activity against A. niger and A. flavus when compared with the standard drugs Norfloxacin and Nystatin at concentrations of 25, 50, 75 and 100 µg/mL. The rest of the title compounds have shown moderate activity against all the bacterial and fungal strains. Molecular docking studies revealed that the synthesized compounds have exhibited significant binding modes with high dock scores ranging from −7.2 to −9.5 against 3V2B protein when compared with the standard drugs Norfloxacin (−5.8) and Nystatin (−6.6) respectively. Hence, it is suggested that the synthesized phosphoramidate derivatives of 6-fluoro-3-(piperidin-4-yl)benzo[ d ]isoxazole will stand as the promising antimicrobial drug candidates in future.