Nimesulide derivatives reduced cell proliferation against breast and ovarian cancer: synthesis, characterization, biological assessment, and crystal structure.

Abstract

New nimesulide derivatives (A1-A6) were synthesized and investigated by IR, 1H NMR, 13C NMR, melting point, elemental analysis, mass spectra, and DSC analysis. Agent A3 single crystal was grown and solved in a monoclinic crystal system with Cc. Heat shock protein 27 (HSP27) and tubulin are essential cellular proteins for normal cell division and growth. In addition, these proteins are expressed highly in cancer cells. Breast cancer (SKBR3) and ovarian cancer (SKOV3) cell lines are our models for biological assessment. The data revealed that nimesulide analogs showed high cytotoxicity when treated with SKBR3 cell line ranges from 0.22 µM to 12.0 µM, while SKOV3 cell line from 0.1 µM to 16.0 µM. In-depth, structure-activity relationship applied on nimesulide lead structure highlights the importance of a bulk moiety on position two that reduces cell proliferation in both cell lines.

Methoxybenzamide derivative of nimesulide from anti-fever to anti-cancer: Chemical characterization and cytotoxicity

“…When a patient is receiving chemotherapy drugs, HSP27 phosphorylation increases tubulin polymerization, proliferation and stops the apoptotic pathways ( Charette and Landry, 2000 , Xi et al, 2015 ). HSP27 promotes cancer cells division and metastasis (Han-Shui et al, 2001; Calderwood et al, 2006 , Casado et al, 2007 ) and is overexpressed in many types of human cancer: including gastric ( Hua et al, 2017 ), liver (Jorg et al, 2017), prostate ( Rocchi et al, 2005 ), rectal ( Haiping et al, 2017 ), lung ( Baowei et al, 2017 ), ovarian ( Jaragh-Alhadad, 2018 , Jaragh-Alhadad et al, 2022 , Jaragh-Alhadad and Ali, 2021 ) and breast cancer ( Calderwood et al, 2006 , Vidyasagar et al, 2012 ) . In addition, to its pronounced treatments’ resistance in breast ( Vidyasagar et al, 2012 ), colon, leukemia ( Ciocca and Calderwood, 2005 ), and ovarian cancers ( Jaragh-Alhadad, 2018 , Jaragh-Alhadad et al, 2022 , Jaragh-Alhadad and Ali, 2021 ) .…”

“…Therefore, the development of old drugs for new and faster therapeutic purposes is urgently required ( Zhang et al, 2020 ) . This strategy provides further benefits because the drug is already administered to patients and no need for further clinical trials ( Mahase, 2019 , Jaragh-Alhadad and Ali, 2021 ) . Therefore, the goal of this study is to use nimesulide as a starting material for the synthesis of agent L1 with new ligands added to its skeleton and spectroscopically characterized ( Jaragh-Alhadad and Ali, 2021 , Jaragh-Alhadad et al, 2022 ).…”

“…This strategy provides further benefits because the drug is already administered to patients and no need for further clinical trials ( Mahase, 2019 , Jaragh-Alhadad and Ali, 2021 ) . Therefore, the goal of this study is to use nimesulide as a starting material for the synthesis of agent L1 with new ligands added to its skeleton and spectroscopically characterized ( Jaragh-Alhadad and Ali, 2021 , Jaragh-Alhadad et al, 2022 ). Finally, the cytotoxic activities of agent L1 were treated with H292, SKOV3, and SKBR3 cancer models.…”