Pyrazoles and Fused Pyrimidines: Synthesis, Structure Elucidation, Antitubercular Activity and Molecular Docking Study

(E-pub Ahead of Print)

Author(s): Amerah M. Al-Soliemy, Rehab Sabour, Thoraya A. Farghaly*

Journal Name: Medicinal Chemistry

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Background: Synthesis of new heterocyclic drugs in short reaction time with sufficient quantity is considered as a target for several pharmaceutical scientists. Thus, organic reactions proceeded on the surface of nano-sized catalysts to speed up the stimulation process. Objective: we aimed in this research to synthesize a new series of heterocyclic compounds carrying pyrazole moiety in the presence of ZnO nano-catalyst to investigate their anti-tubercular activity.

Methods: ZnO(NPs) was used in synthesis of novel series of thienylpyrazolopyrimidines bearing arylazo group by reaction of thiophene-enaminone and the amino-arylazopyrazoles in excellent yield. On the other hand, another series of theinyl-pyrazoles was synthesized through the reaction of the same enaminone with hydrazonoyl chlorides but the usage of ZnO(NPs) failed in such reactions.

Results: The proposed structures of the products and the mechanistic pathways of the reactions were assured based on the spectral data and chemical evidences. Thienylpyrazole derivatives were assessed for their activity as Mycobacterium tuberculosis inhibitor and their results revealed that two thienylpyrazole derivatives 24d & 24f showed the most significant anti-mycobacterial activity with MIC values 0.70 & 1.29 µM/mL, respectively comparing with the MIC value = 0.60 µM/mL of the standard drug Rifampicin. Furthermore, the most active thienylpyrazole derivatives were investigated for their cytotoxic impact versus normal cells WI-38 (Normal human Lung fibroblast cells) using MTT assay. These thienylpyrazole derivatives exhibited good selective index profile. Moreover, 1,3,4-trisubstituted pyrazole analogues showed good interaction with the active site of enoyl-acyl carrier protein reductase (Mt InhA) through the molecular docking studies.

Conclusion: We succeeded to synthesis a new series of heterocyclic compounds carrying pyrazole moiety in the presence of ZnO nano-catalyst as anti-tubercular agents.

Keywords: Pyazoles, fused pyrimidines, antitubercular activity, enaminones, hydrazonoyl halides, Molecular docking.

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Article Details

Published on: 24 March, 2021
(E-pub Ahead of Print)
DOI: 10.2174/1573406417666210324131951

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