Designing Functionally Substituted Pyridine-Carbohydrazides for Potent Antibacterial and Devouring Antifungal Effect on Multidrug Resistant (MDR) Strains

Abstract

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.

Base catalyzed one-pot thia-Michael addition-oxidation reaction of hetero-aromatic thiols to 2-aryl-3-nitro-2H-chromenes and their antibacterial evaluation

“…12,13 Moreover, the pyrimidine and pyridine cores have been recognized as key scaffolds owing to their potent antibacterial activities. [14][15][16] As such, owing to these unique biological and pharmacological characteristics, we explored the Michael addition of sulfur-nitrogen-containing heterocyclic scaffolds with medicinally active 2-aryl-3-nitro-2H-chromene derivatives. 17,18 Note that our group has already reported aza/carba-Michael addition reactions with 3-nitro-2H-chromene derivatives and examined the antibacterial properties.…”

“…12,13 Moreover, the pyrimidine and pyridine cores have been recognized as key scaffolds owing to their potent antibacterial activities. 14–16…”

Design, green synthesis, and quorum sensing quenching potential of novel 2-oxo-pyridines containing a thiophene/furan scaffold and targeting a LasR gene on P. aeruginosa

“…32 In addition, the pyridinone nucleus displayed in a numerous of drugs, such as Gimeracil (DPD inhibitor that used in treatment of cancer), Deferiprone (an iron chelator), Pirfenidone (antibrotic agent used to treat idiopathic pulmonary brosis (IPF)), Doravirine (a drug used to treat HIV), and Ciclopirox (broad spectrum antifungal agent). [33][34][35][36] Interest is increased toward antibiotics containing the pyridine nucleus, such as Pristinamycin, Ozenoxacin, and Tedizolid (used to treat Staphylococcal infections), Prothionamide and Ethionamide (used to treat tuberculosis (TB)), Nalidixic acid, Levooxacin, Ciprooxacin, and Ceazidime (used to treat Pseudomonas aeruginosa infections) [37][38][39] Fig. 1.…”

Synthesis of Acyl Hydrazides from Carboxamides and Hydrazine Hydrate Under Metal‐Free Conditions at Room Temperature

“…Acyl hydrazides are a very important class of organic compounds [1–2] with a wide spectrum of biological activities, including antituberculous, [3–6] anticonvulsant, [7] antidepressant, [8] anti‐inflammatory, [9] antimalarial, [10] anticancer, [12] antimycobacterial, [11] antituberculous, [13] etc. Acyl hydrazide derivatives are clinically used as antituberculous (isoniazid), antidepressant (iproniazid and marplan), antibacterial drugs (Figure 1), etc [14–18] . Moreover, acyl hydrazides found different applications in the field of herbicides, polymers, chemical preservers, etc [19] .…”

“…Acyl hydrazide derivatives are clinically used as antituberculous (isoniazid), antidepressant (iproniazid and marplan), antibacterial drugs (Figure 1), etc. [14][15][16][17][18] Moreover, acyl hydrazides found different applications in the field of herbicides, polymers, chemical preservers, etc. [19] On the other hand, acyl hydrazides are valuable synthons and intermediates in organic chemistry.…”