Novel N-bridged pyrazole-1-carbothioamides with potential antiproliferative activity: design, synthesis, in vitro and in silico studies

Islam H El Azab; Essa M Saied; Alaa A Osman; Amir E Mehana; Hosam A Saad; Nadia Aa Elkanzi

doi:10.4155/fmc-2021-0066

Novel N-bridged pyrazole-1-carbothioamides with potential antiproliferative activity: design, synthesis, in vitro and in silico studies

Future Med Chem. 2021 Oct;13(20):1743-1766. doi: 10.4155/fmc-2021-0066. Epub 2021 Aug 24.

Authors

Islam H El Azab^{1

2}, Essa M Saied^{3

4}, Alaa A Osman⁵, Amir E Mehana⁶, Hosam A Saad⁷, Nadia Aa Elkanzi^{2

8}

Affiliations

¹ Department of Chemistry, College of Science, Taif University, PO Box 11099, Taif, 21944, Saudi Arabia.
² Department of Chemistry, Faculty of Science, Aswan University, Aswan, PO Box 81528, Aswan, Egypt.
³ Department of Chemistry, Faculty of Science, Suez Canal University, Ismailia, 41522, Egypt.
⁴ Institute for Chemistry, Humboldt Universität zu Berlin, Brook-Taylor-Str. 2, Berlin, 12489, Germany.
⁵ Department of Pharmaceutical Chemistry, Faculty of Pharmacy, New Giza University, Cairo, Egypt.
⁶ Zoology Department, Faculty of Science, Suez Canal University, Ismailia, 41522, Egypt.
⁷ Department of Chemistry, College of Science, Taif University, PO Box 11099, Taif, 21944, Saudi Arabia.
⁸ Chemistry Department, College of Science, Jouf University, PO Box 2014, Sakaka, Saudi Arabia.

PMID: 34427113
DOI: 10.4155/fmc-2021-0066

Abstract

Thiazole-substituted pyrazole is an important structural feature of many bioactive compounds, including antiviral, antitubercular, analgesic and anticancer agents. Herein we describe an efficient and facile approach for the synthesis of two series of 36 novel N-bridged pyrazole-1-phenylthiazoles. The antiproliferative activity of a set of representative compounds was evaluated in vitro against different human cancer cell lines. Among the identified compounds, compound 18 showed potent anticancer activity against the examined cancer cell lines. The in silico molecular docking study revealed that compound 18 possesses high binding affinity toward both SK1 and CDK2. Overall, these results indicate that compound 18 is a promising lead anticancer compound which may be exploited for development of antiproliferative drugs.

Keywords: 1,2,4-triazole; CDK2; N-bridged heterocycles; SK1; anticancer activity; apoptosis; molecular docking; pyrazole-1-phenylthiazoles.

Publication types

Research Support, Non-U.S. Gov't

MeSH terms

Antineoplastic Agents / chemical synthesis
Antineoplastic Agents / chemistry
Antineoplastic Agents / pharmacology*
Bridged-Ring Compounds / chemical synthesis
Bridged-Ring Compounds / chemistry
Bridged-Ring Compounds / pharmacology*
Cell Proliferation / drug effects
Drug Design*
Drug Screening Assays, Antitumor
Humans
Molecular Docking Simulation
Molecular Structure
Protein Kinase Inhibitors / chemical synthesis
Protein Kinase Inhibitors / chemistry
Protein Kinase Inhibitors / pharmacology*
Protein Kinases / metabolism
Thiazoles / chemical synthesis
Thiazoles / chemistry
Thiazoles / pharmacology*
Tumor Cells, Cultured

Substances

Antineoplastic Agents
Bridged-Ring Compounds
Protein Kinase Inhibitors
Thiazoles
Protein Kinases