Novel 6-Phenylnicotinohydrazide Derivatives: Design, Synthesis and Biological Evaluation as a Novel Class of Antitubercular and Antimicrobial Agents

• Published in: Biological & pharmaceutical bulletin Vol. 40; no. 11; pp. 1883 - 1893
• Main Authors: Soliman, Dalia Hussein, Eldehna, Wagdy Mohamed, Ghabbour, Hazem Ahmed, Kabil, Maha Mamdouh, Abdel-Aziz, Marwa Mostafa, Abdel-Aziz, Hatem Abdel-Kader
• Format: Journal Article
• Language: English
• Published: Japan The Pharmaceutical Society of Japan 2017; Japan Science and Technology Agency
• Subjects: 6-phenylnicotinohydrazide; Antifungal Agents - chemical synthesis; Antifungal Agents - pharmacology; antimicrobial; Antimicrobial activity; Antimicrobial agents; antitubercular; Antitubercular agents; Antitubercular Agents - chemical synthesis; Antitubercular Agents - pharmacology; Breast cancer; Cell Line; Cytotoxicity; Design analysis; Drug Design; Evaluation; Fungicides; Humans; Hydrazines - chemical synthesis; Hydrazines - pharmacology; Microbial Sensitivity Tests; Microorganisms; Minimum inhibitory concentration; Mycobacterium tuberculosis - drug effects; Nicotinic Acids - chemical synthesis; Nicotinic Acids - pharmacology; Selectivity; Structure-Activity Relationship; synthesis; synthesis; antimicrobial; antitubercular; cytotoxicity; 6-phenylnicotinohydrazide
• ISSN: 0918-6158; 1347-5215
• DOI: 10.1248/bpb.b17-00361

In our ongoing efforts to develop potent antitubercular agents based on the 6-phenylnicotinohydrazide, herein we report the design, synthesis and biological evaluation of three sets of 6-phenylnicotinohydrazide derivatives 8a–g, 12 and 16a, b. The designed compounds were synthesized and in vitro evaluated for their antitubercular activity. In addition, their antifungal and antibacterial activities were evaluated as well. The nicotinohydrazide class displayed different levels of antimicrobial activity and possessed a distinctive pattern of selectivity against the tested microorganisms. However, the 2,6-dichlorobenzylidene counterpart 8b emerged as the most active one in this study, with superior antimycobacterial activity (minimum inhibitory concentration (MIC)=3.90 µg/mL) and potent broad-spectrum antimicrobial activities with MIC range of 0.24–1.95 µg/mL. The structure–activity relationship for such nicotinohydrazides has been established. Further, the cytotoxicity of the most active antitubercular compounds 8b, d and g were tested against the normal breast cells WI-38; none of them displayed significant cytotoxic effect, thereby providing a good therapeutic index.