title: Synthesis of novel 4-nitropyrrole-based semicarbazide and thiosemicarbazide hybrids with antimicrobial and anti-tubercular activity.
abstract: We report the synthesis and screening of forty novel 4-nitropyrrole-semicarbazide conjugates inspired from the reported bio-potential of bromopyrrole alkaloids and semicarbazide derivatives for antimicrobial activity. Herein, hybrids 5k-5o, 5r, 5s and 5t displayed four-fold increased activity (MIC=0.39 μg/mL) against Escherichia coli compared to standard ciprofloxacin. Eight hybrids, 5k-5o and 5r-5t displayed equal antibacterial activity (MIC=1.56 μg/mL) against Klebsiella pneumonia compared to standard ciprofloxacin. Hybrid, 5k-5o (MIC=0.195 μg/mL) displayed highly potent antibacterial activity against MSSA as compared to standard ciprofloxacin. Eight-fold superior activity was observed for four hybrids 5k-5m and 5o (MIC=0.39 μg/mL) against MRSA. Further, nine hybrids displayed four-fold superior antifungal activity (MIC=0.78 μg/mL) compared to standard Amphotericin B. Encouraging MICs of these hybrids recognize them as promising leads for development of potential antimicrobial drugs.
authors.affiliation: Discipline of Pharmaceutical Sciences, College of Health Sciences, University of KwaZulu-Natal, Durban 4001, South Africa.
authors.forename: Rajesh A
authors.initials: RA
authors.lastname: Rane
authors.affiliation: Piramal Health Care Ltd, Goregaon, Mumbai, India.
authors.forename: Shital S
authors.initials: SS
authors.lastname: Naphade
authors.affiliation: S.P.P. School of Pharmacy and Technology Management, NMIMS University, Vile Parle, Mumbai 400056, India.
authors.forename: Pavan Kumar
authors.initials: PK
authors.lastname: Bangalore
authors.affiliation: Discipline of Pharmaceutical Sciences, College of Health Sciences, University of KwaZulu-Natal, Durban 4001, South Africa.
authors.forename: Mahesh B
authors.initials: MB
authors.lastname: Palkar
authors.affiliation: Discipline of Pharmaceutical Sciences, College of Health Sciences, University of KwaZulu-Natal, Durban 4001, South Africa.
authors.forename: Mahamadhanif S
authors.initials: MS
authors.lastname: Shaikh
authors.affiliation: Discipline of Pharmaceutical Sciences, College of Health Sciences, University of KwaZulu-Natal, Durban 4001, South Africa. Electronic address: karpoormath@ukzn.ac.za.
authors.forename: Rajshekhar
authors.initials: R
authors.lastname: Karpoormath
mesh_terms: D000900:Anti-Bacterial Agents / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology*; D000995:Antitubercular Agents / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology; D004305:Dose-Response Relationship, Drug; D004926:Escherichia coli / Q000187:drug effects; D007711:Klebsiella pneumoniae / Q000187:drug effects; D008826:Microbial Sensitivity Tests; D015394:Molecular Structure; D009169:Mycobacterium tuberculosis / Q000187:drug effects; D011758:Pyrroles / Q000737:chemistry*; D012663:Semicarbazides / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology*; D013211:Staphylococcus aureus / Q000187:drug effects; D013329:Structure-Activity Relationship
chemical_list: C000591459:4-nitropyrrole; D000900:Anti-Bacterial Agents; D000995:Antitubercular Agents; D011758:Pyrroles; D012663:Semicarbazides
keywords: 4-Nitropyrrole; Anti-tubercular agent; Antimicrobial agent; Semicarbazides; Thiosemicarbazides