Synthesis of new bis‐pyrazole linked hydrazides and their in vitro evaluation as antimicrobial and anti‐biofilm agents: A mechanistic role on ergosterol biosynthesis inhibition in Candida albicans

Abstract

Literature reports suggest that pyrazoles and hydrazides are potential antimicrobial pharmocophores. Considering this fact, a series of nineteen conjugates containing hybrids of bis‐pyrazole scaffolds joined through a hydrazide linker were synthesized and further evaluated for their antimicrobial activity against a panel of Gram‐positive and Gram‐negative bacteria along with Candida albicansMTCC 3017 strain. Although the derivatives exhibited good antibacterial activity, some of the derivatives (13d, 13j, 13l, 13p, and 13r) showed excellent anti‐Candida activity with MICs values of 3.9 μg/ml, which was equipotent to that of the standard Miconazole (3.9 μg/ml), which has inspired us to further explore their anti‐Candida activity. The same compounds were also tested for anti‐biofilm studies against various Candida strains and among them, compounds 13l and 13r efficiently inhibited the formation of fungal biofilms. Field emission scanning electron micrographs revealed that one of the promising compound 13r showed cell damage and in turn cell death of the Candida strain. These potential conjugates (13l and 13r) also demonstrated promising ergosterol biosynthesis inhibition against some of the strains C. albicans, which were further validated through molecular docking studies. In silico computational studies were carried out to predict the binding modes and pharmacokinetic parameters of these conjugates.

Synthesis, antimicrobial and ergosterol biosynthesis inhibition activity of clubbed 1,1′-biphenyl-pyrazole derivatives

“…2) have been reported to have significant antifungal activities by the inhibition of ergosterol biosynthesis. 36–39…”

“…2) have been reported to have significant antifungal activities by the inhibition of ergosterol biosynthesis. [36][37][38][39] The literature reveals that 1,1 0 -biphenyl derivatives clubbed with the 2-position of the thiazole ring show significant antimicrobial activity. 40,41 The 1,3-or 3,5-diphenyl pyrazole compounds have been reported for antimicrobial activity.…”

Synthesis, Characterization, and Biological Study of 3‐Trifluoromethylpyrazole Tethered Chalcone‐Pyrrole and Pyrazoline‐Pyrrole Derivatives

“…Celecoxib can diminish the possibility of indication and the progression of different types of cancer, mainly breast cancer [20] . In the view of anticancer potency, the literature review suggests that pyrazole could be used as a significant moiety in the design of novel anticancer agents [21,22] …”

“…[20] In the view of anticancer potency, the literature review suggests that pyrazole could be used as a significant moiety in the design of novel anticancer agents. [21,22] On the other hand, chalcones (compounds A-C: VEGFR-2 kinase inhibitors, Figure 1), [23] pyrazolines (e. g., axitinib and compound E: tyrosine kinase inhibitor, compound D: c-Src inhibitor, Figure 1), [24 -26] and pyrroles (semaxanib and sunitinib, Figure 1, as VEGFR-2 kinase inhibitors) moieties [27,28] have been established as potent scaffolds for drug design and also, their efficiencies have been proved in our previous work. [29,30] All the above-described findings have been encouraged us to develop a novel series of chalcones and that condensed with substituted pyrazoline derivatives.…”