Green Chemistry and In silico Techniques for Synthesis of Novel
Pyranopyrazole and Pyrazolo-pyrano-pyrimidine Derivatives as
Promising Antifungal Agents

Kalyani   Dhirendra   Asgaonkar; Trupti   Sameer   Chitre; Shital   Manoj   Patil; Krishna   Sambhajirao   Shevate; Ashwini   Kishan   Sagar; Dipti   Dattatray   Ghate; Parth   Anil   Shah

doi:10.2174/0127724344269458231124123935

Abstract

Background: Every year Invasive Fungal Infections (IFI) are globally affecting millions of people. Candida albicans and Aspergillus niger have been reported as the most infectious and mortality-inducing fungal strains among all pathogenic fungi.

Aims & Objectives: To tackle this problem in the current study Pyranopyrazoles and Pyrazolopyrano- pyrimidine derivatives were developed using molecular hybridization, green chemistry and one-pot multicomponent reaction.

Materials and Methods: In the present work, New Chemical entities (NCE’s) were developed on the basis of Structure activity relationship. All designed NCE’s were screened for ADMET studies using the QikProp module of Schrodinger software. NCE’s with zero violations were further docked on the crystal structure of 14α demethylase, cytochrome P450 and thymidine synthase (PDB ID: 5V5Z, 7SHI, 1BID). Selected molecules were synthesized using green chemistry techniques and evaluated for in vitro antifungal activity against Candida albicans and Aspergillus niger.

Results and Discussion: Designed NCE’s (B1-12 and C1-11) showed favorable results in ADMET studies. In the docking study six compounds from series-B and five molecules from series- C showed good dock score and binding interaction when compared with the standard drugs. Compounds B-3 and C-4 showed the highest zone of inhibition activity against Candida albicans, where as B-1 and C-3 had shown highest zone of inhibition activity against Aspergillus niger.

Conclusion: Bicyclic ring (series B) showed better activity as compare to fused tricyclic ring (series C).

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Green Chemistry and In silico Techniques for Synthesis of Novel Pyranopyrazole and Pyrazolo-pyrano-pyrimidine Derivatives as Promising Antifungal Agents

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