Synthesis, Antiproliferative Evaluation, and Molecular Docking of Thieno[3,2-e]indazole Derivatives

Rafat   M.   Mohareb; Ibram   Refat   Mikhail; Marwa   Soliman   Gamaan; Ensaf   S.   Alwan

doi:10.2174/0115701808287763240302165049

Abstract

Background: Although indazole derivatives are rare and may not be available easily in nature, there are many reports demonstrating their pharmaceutical and other applications.

Objective: This study aimed to synthesize new indazole derivatives and evaluate their antiproliferative activity to produce new anti-cancer agents.

Methods: Compounds 3a-c were synthesized through the reaction. The 2-aryllidenecyclohexane-1,3- dione derivatives 3a-c were obtained through the reaction of cyclohexane-1,3-dione with aromatic aldehydes used for the synthesis of thieno-[3,2-e]indazole derivatives. These derivatives were characterized by extensive analytical and spectral studies and were further used as starting materials for some heterocyclic transformations to produce biologically active compounds. The antiproliferative activities of the newly synthesized compounds were evaluated against the six cancer cell lines, A549, HT-29, MKN-45, U87MG, SMMC-7721, and H460. Most of the tested compounds exhibited high cytotoxicity except a few compounds.

Results: In this study, new compounds were synthesized, characterized, and evaluated toward the selected six cancer cell lines. All tested compounds displayed potent c-Met enzymatic activity with IC50 values ranging from 0.25 to 10.30 nM and potent prostate PC-3 cell line inhibition with IC50 values ranging from 0.17 to 9.31 μM.

Conclusion: The results obtained in this work demonstrated that the variations in substituents within the aryl moiety, together with the attached heterocyclic ring, have a notable influence on the antiproliferative activity. The results obtained in this work encourage further work in the future.

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Letters in Drug Design & Discovery

Synthesis, Antiproliferative Evaluation, and Molecular Docking of Thieno[3,2-e]indazole Derivatives

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