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

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 pro-ceeded 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) were used in the synthesis of novel series of thienylpyrazolopyrimidines bear-ing arylazo group by the reaction of thiophene-enaminone and the amino-arylazopyrazoles in excel-lent yield. On the other hand, another series of theinyl-pyrazoles was synthesized through the reac-tion 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 as-sessed 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 mu M/mL, respectively comparing with the MIC value = 0.60 mu M/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 analogs showed good interaction with the active site of enoyl-acyl carri-er protein reductase (Mt InhA) through molecular docking studies. Conclusion: We synthesized a new series of heterocyclic compounds carrying pyrazole moiety in the presence of ZnO nano-catalyst as anti-tubercular agents.

Automated summary

In this research, a new series of heterocyclic compounds carrying pyrazole moiety were successfully synthesized using ZnO nano-catalyst. The synthesized compounds showed significant anti-tubercular activity and good selective index profile. Furthermore, molecular docking studies revealed their good interaction with the active site of the target protein.