Design, molecular modeling, synthesis and biological evaluation of novel pyrazole based schiff Bases as fungal biofilm inhibitors

Manoj Gangadhar Damale, Santosh Subash Chajjed, Santosh Dattatreya Shelke, Rajendra Harischandra Patil,
Jaiprakash Navnath Sangshetti

Dr. Rafiq Zakaria Campus, Y.B. Chavan College of Pharmacy, Aurangabad, Maharashtra, India

Refer this article

Manoj Gangadhar Damale,Santosh Subash Chajjed, Santosh Dattatreya Shelke, Rajendra Harischandra. Patil,Jaiprakash Navnath Sangshetti, 2022. Design, Molecular modeling, Synthesis and Biological evaluation of Novel Pyrazole based Schiff Bases as fungal Biofilm Inhibitors. Journal of medical pharmaceutical and allied sciences. V 11 - I4, Pages – 5108 - 5120 Doi: 10.55522/jmpas.V11I4.3068.

ABSTRACT

We designed series of pyrazole based Schiff bases on the basis of Bioisosteric replacement principle and validated for drug likeness using Absorption, Distribution, Metabolism, and Excretion (ADMET) criteria. The designed Schiff bases who have excellent pharmacokinetics properties, Low toxicity when In-silico analyzed for inhibition potential using molecular docking study. The top hit of molecular docking having free energy of binding in between -6.95to -4.28 kcal/mol was synthesized and biologically evaluated for fungal biofilm inhibition and minimum inhibitory concentration. The invitro biological assay of synthesized Schiff bases suggesting antibiofilm activity of Schiff base MPY10 inhibitory concentration (IC50=41.7μM) and MPY1 (IC50=44.7μM) very much equivalent to standard drug Fluconazole. The inhibition potential of MPY10 (MIC=42.6μg), MPY1 (MIC=54.4μg), MPY2 (MIC=58.1μg), MPY6 (MIC=61.8μg) and MPY4 (MIC=64.2μg) reproduces the molecular docking results shown against c. albicans biofilm drug target secreted aspartic proteinases (Sap5) signifying antifungal activity as that of standard.

Keywords:

Schiff bases, Secreted aspartic proteases (Saps), Biofilm, Pharmacokinetics properties, Molecular docking, Antifungal assay

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