Development of novel isatin-nicotinohydrazide hybrids with potent activity against susceptible/resistant Mycobacterium tuberculosis and bronchitis causing-bacteria.

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.

• Authors: Zainab M Elsayed, Wagdy M Eldehna, Marwa M Abdel-Aziz, Mahmoud A El Hassab, Eslam B Elkaeed, Tarfah Al-Warhi, Hatem A Abdel-Aziz, Sahar M Abou-Seri, Eman R Mohammed
• Journal: Journal of enzyme inhibition and medicinal chemistry (J Enzyme Inhib Med Chem) Vol. 36 Issue 1 Pg. 384-393 (Dec 2021) ISSN: 1475-6374 [Electronic] England
• PMID: 33406941 (Publication Type: Journal Article)

Chemical References

• Anti-Bacterial Agents
• Bacterial Proteins
• Hydrazines
• Isatin
• Alcohol Oxidoreductases
• DprE1 protein, Mycobacterium tuberculosis
• Isoniazid
• Streptomycin

Topics

• Alcohol Oxidoreductases (antagonists & inhibitors, chemistry, metabolism)
• Anti-Bacterial Agents (chemical synthesis, pharmacology)
• Bacterial Proteins (antagonists & inhibitors, chemistry, metabolism)
• Binding Sites
• Bordetella pertussis (chemistry, enzymology, isolation & purification)
• Bronchitis (drug therapy, microbiology)
• Drug Design
• Drug Resistance, Bacterial (drug effects, genetics)
• Haemophilus influenzae (chemistry, enzymology, isolation & purification)
• Hydrazines (chemistry)
• Isatin (chemistry)
• Isoniazid (pharmacology)
• Klebsiella pneumoniae (chemistry, enzymology, isolation & purification)
• Microbial Sensitivity Tests
• Molecular Docking Simulation
• Moraxella catarrhalis (chemistry, enzymology, isolation & purification)
• Mycobacterium tuberculosis (chemistry, enzymology, isolation & purification)
• Protein Binding
• Protein Conformation
• Protein Interaction Domains and Motifs
• Streptococcus pneumoniae (chemistry, enzymology, isolation & purification)
• Streptomycin (pharmacology)
• Structure-Activity Relationship
• Tuberculosis (drug therapy, microbiology)