Cp2ZrCl2: AN EFFICIENT CATALYST FOR MULTICOMPONENT SYNTHESIS OF CAROTENOID DEHYDROSQUALENE SYNTHASE INHIBITING PYRANO[2,3-d]PYRIMIDINEDIONES

BABASAHEB D SONAWANE; VIKAS D D SONAWANE; KAILAS D SONAWANE; MARUTI D J DHANAVADE; CHETAN B AWARE; SHARAD K AWATE; SURESH V PATIL

doi:10.22159/ajpcr.2019.v12i2.26862

Authors

BABASAHEB D SONAWANE Department of Chemistry, Karmaveer Bhaurao Patil Mahavidyalaya, Pandharpur, Maharashtra, India.
VIKAS D D SONAWANE Department of Chemistry, Smt. Kusumtai Rajarambapu Patil Kanya Mahavidyalaya, Islampur, Maharashtra, India.
KAILAS D SONAWANE Department of Microbiology Shivaji University, Kolhapur, Maharashtra, India.
MARUTI D J DHANAVADE Department of Microbiology Shivaji University, Kolhapur, Maharashtra, India.
CHETAN B AWARE Department of Biotechnology, Shivaji University, Kolhapur, Maharashtra, India.
SHARAD K AWATE Department of Chemistry, Karmaveer Bhaurao Patil Mahavidyalaya, Pandharpur, Maharashtra, India.
SURESH V PATIL Department of Chemistry, Karmaveer Bhaurao Patil Mahavidyalaya, Pandharpur, Maharashtra, India.

DOI:

https://doi.org/10.22159/ajpcr.2019.v12i2.26862

Keywords:

Zirconocene dichloride, Pyrano[2,3-d]pyrimidinediones, Antimicrobial, Antioxidant, Carotenoid dehydrosqualene synthase, Molecular docking

Abstract

Objectives: The present protocol deals with zirconocene dichloride (Cp2ZrCl2) catalyzed synthesis of pyrano[2,3-d]pyrimidinediones through one-pot multicomponent reactions of aromatic aldehydes with malononitrile and barbituric acid at ambient temperature. All the synthesized compounds were characterized and evaluated for antibacterial, antifungal, and antioxidant activities. Furthermore, a molecular docking was carried out to reveal the atomic insights between synthesized compounds and carotenoid dehydrosqualene synthase (PDB ID: 3ACX).

Methods: All the synthesized compounds were evaluated for their in vitro antimicrobial activity by diffusion method. Antioxidant activities such as 1,1-diphenyl-2-picrylhydrazyl and radical scavenging activity. A mixture of barbituric acid 1 (1 mmol), malononitrile 2 (1 mmol), benzaldehyde 3a (1 mmol), ethanol (5 mL), and Cp2ZrCl2 (5 mol %) was stirred at ambient temperature for specified time. After completion of reaction as indicated by thin-layer chromatography, the obtained crude product was filtered and purified by column chromatography on silica gel (Merck, 60–120 mesh) using ethyl acetate:pet. ether to afford pure product which was then characterized by spectroscopic methods such by FTIR, nuclear magnetic resonance (1H NMR), 13C NMR, and mass spectroscopy.

Results: All the synthesized pyrano[2,3-d]pyrimidinediones were characterized by spectroscopic analysis. The results revealed that pyrano[2,3-d] pyrimidinediones (4 a-k) displayed the zone of inhibition in the range of 3–13 mm. The most active compound 4b displayed largest zone of inhibition of 13 mm for Escherichia coli (NCIM-2832) and 9 mm for Bacillus subtilis (NCIM-2635). The antifungal and antioxidant activity of all synthesized pyrano[2,3-d]pyrimidinediones (4a-k) showed moderate to good activity. Molecular docking studies suggest that pyrano[2,3-d]pyrimidinediones might inhibit the carotenoid dehydrosqualene synthase activity.

Conclusion: All the synthesized pyrano[2,3-d]pyrimidinediones display moderate to good antibacterial, antifungal, and antioxidant activity. This molecular docking studies supported that pyrano[2,3-d]pyrimidinediones might inhibit the carotenoid dehydrosqualene synthase (PDB ID: 3ACX).

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Author Biography

BABASAHEB D SONAWANE, Department of Chemistry, Karmaveer Bhaurao Patil Mahavidyalaya, Pandharpur, Maharashtra, India.

Associate Professor

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