Development of novel isatin–nicotinohydrazide hybrids with potent activity against susceptible/resistant Mycobacterium tuberculosis and bronchitis causing–bacteria. (1st January 2021)

• Record Type: Journal Article
• Authors: Elsayed, Zainab M.; Eldehna, Wagdy M.; Abdel-Aziz, Marwa M.; El Hassab, Mahmoud A.; Elkaeed, Eslam B.; Al-Warhi, Tarfah; Abdel-Aziz, Hatem A.; Abou-Seri, Sahar M.; Mohammed, Eman R.
• Is Part Of: Journal of enzyme inhibition and medicinal chemistry. Volume 36:Number 1(2021)
• Page Start: 384
• Page End: 392
• Publication Date: 2021-01-01
• Subjects: Anti-tubercular activity -- DprE1 inhibitors -- resistant TB -- nicotinohydrazide -- isatin derivatives; Enzyme inhibitors -- Periodicals; Enzyme Inhibitors -- periodicals; Biochemistry -- periodicals; 572.7
• DOI: 10.1080/14756366.2020.1868450
• Languages: English
• ISSNs: 1475-6366

Abstract

Abstract: Joining the global fight against Tuberculosis, the world's most deadly infectious disease, herein we present the design and synthesis of novel isatin-nicotinohydrazide hybrids (5a–m and 9a–c ) as promising anti-tubercular and antibacterial agents. The anti-tubercular activity of the target hybrids was evaluated against drug-susceptible M. tuberculosis strain (ATCC 27294) where hybrids 5d, 5g and 5h were found to be as potent as INH with MIC = 0.24 µg/mL, also the activity was evaluated against Isoniazid/Streptomycin resistant M. tuberculosis (ATCC 35823) where compounds 5g and 5h showed excellent activity (MIC = 3.9 µg/mL). Moreover, the target hybrids were examined against six bronchitis causing-bacteria. Most derivatives exhibited excellent antibacterial activity. K. pneumonia emerged as the most sensitive strain with MIC range: 0.49–7.81 µg/mL. Furthermore, a molecular docking study has proposed DprE1 as a probable enzymatic target for herein reported isatin-nicotinohydrazide hybrids, and explored the binding interactions within the vicinity of DprE1 active site. GRAPHICAL ABSTRACT: UF0001