Designing Functionally Substituted Pyridine-Carbohydrazides for Potent Antibacterial and Devouring Antifungal Effect on Multidrug Resistant (MDR) Strains
Farooq-Ahmad Khan,
Sana Yaqoob,
Shujaat Ali,
Nimra Tanveer,
Yan Wang,
Sajda Ashraf,
Khwaja Ali Hasan,
Shaden A. M. Khalifa,
Qiyang Shou,
Zaheer Ul-Haq,
Zi-Hua Jiang,
Hesham R. El-Seedi
Affiliations
Farooq-Ahmad Khan
Third World Center for Science and Technology, International Center for Chemical and Biological Sciences, University of Karachi, Karachi 75270, Pakistan
Sana Yaqoob
Third World Center for Science and Technology, International Center for Chemical and Biological Sciences, University of Karachi, Karachi 75270, Pakistan
Shujaat Ali
Third World Center for Science and Technology, International Center for Chemical and Biological Sciences, University of Karachi, Karachi 75270, Pakistan
Nimra Tanveer
Third World Center for Science and Technology, International Center for Chemical and Biological Sciences, University of Karachi, Karachi 75270, Pakistan
Yan Wang
H.E.J. Research Institute of Chemistry, International Center for Chemical and Biological Sciences, University of Karachi, Karachi 75270, Pakistan
Sajda Ashraf
H.E.J. Research Institute of Chemistry, International Center for Chemical and Biological Sciences, University of Karachi, Karachi 75270, Pakistan
Khwaja Ali Hasan
Molecular and Structural Biology Research Laboratory, Department of Biochemistry, University of Karachi, Karachi 75270, Pakistan
Shaden A. M. Khalifa
Department of Molecular Biosciences, The Wenner-Gren Institute, Stockholm University, S-106 91 Stockholm, Sweden
Qiyang Shou
Second Clinical Medical College, Zhejiang Chinese Medical University, Hangzhou 310053, China
Zaheer Ul-Haq
Dr. Panjwani Center for Molecular Medicine and Drug Research, International Center for Chemical and Biological Sciences, University of Karachi, Karachi 75270, Pakistan
Zi-Hua Jiang
Department of Chemistry, Lakehead University, 955 Oliver Road, Thunder Bay, Ontario P7B 5E1, Canada
Hesham R. El-Seedi
International Research Center for Food Nutrition and Safety, Jiangsu University, Zhenjiang 212013, China
The emergence of multidrug-resistant (MDR) pathogens and the gradual depletion of available antibiotics have exacerbated the need for novel antimicrobial agents with minimal toxicity. Herein, we report functionally substituted pyridine carbohydrazide with remarkable antimicrobial effect on multi-drug resistant strains. In the series, compound 6 had potent activity against four MDR strains of Candida spp., with minimum inhibitory concentration (MIC) values being in the range of 16–24 µg/mL and percentage inhibition up to 92.57%, which was exceptional when compared to broad-spectrum antifungal drug fluconazole (MIC = 20 µg/mL, 81.88% inhibition). Substitution of the octyl chain in 6 with a shorter butyl chain resulted in a significant anti-bacterial effect of 4 against Pseudomonas aeruginosa (ATCC 27853), the MIC value being 2-fold superior to the standard combination of ampicillin/cloxacillin. Time-kill kinetics assays were used to discern the efficacy and pharmacodynamics of the potent compounds. Further, hemolysis tests confirmed that both compounds had better safety profiles than the standard drugs. Besides, molecular docking simulations were used to further explore their mode of interaction with target proteins. Overall results suggest that these compounds have the potential to become promising antimicrobial drugs against MDR strains.
