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Exploration of Benzenesulfonamide-Bearing Imidazole Derivatives Activity in Triple-Negative Breast Cancer and Melanoma 2D and 3D Cell Cultures.

ABSTRACT: Heterocyclic compounds are one of the main groups of organic compounds possessing wide range of applications in various areas of science and their derivatives are present in many bioactive structures. They display a wide variety of biological activities. Recently, more and more attention has been focused to such heterocyclic compounds as azoles. In this work, we have synthesized a series of new imidazole derivatives incorporating a benzenesulfonamide moiety in their structure, which then were evaluated for their cytotoxicity against human triple-negative breast cancer MDA-MB-231 and human malignant melanoma IGR39 cell lines by MTT assay. Benzenesulfonamide-bearing imidazole derivatives containing 4-chloro and 3,4-dichlorosubstituents in benzene ring, and 2-ethylthio and 3-ethyl groups in imidazole ring have been determined as the most active compounds. Half-maximal effective concentration (EC₅₀) of the most cytotoxic compound was 27.8 ± 2.8 µM against IGR39 cell line and 20.5 ± 3.6 µM against MDA-MB-231 cell line. Compounds reduced cell colony formation of both cell lines and inhibited the growth and viability of IGR39 cell spheroids more efficiently compared to triple-negative breast cancer spheroids.

SUBMITTER: Balandis B

PROVIDER: S-EPMC8625351 | biostudies-literature | 2021 Nov

REPOSITORIES: biostudies-literature

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Exploration of Benzenesulfonamide-Bearing Imidazole Derivatives Activity in Triple-Negative Breast Cancer and Melanoma 2D and 3D Cell Cultures.

Balandis Benas B Mickevičius Vytautas V Petrikaitė Vilma V

Pharmaceuticals (Basel, Switzerland) 20211113 11

Heterocyclic compounds are one of the main groups of organic compounds possessing wide range of applications in various areas of science and their derivatives are present in many bioactive structures. They display a wide variety of biological activities. Recently, more and more attention has been focused to such heterocyclic compounds as azoles. In this work, we have synthesized a series of new imidazole derivatives incorporating a benzenesulfonamide moiety in their structure, which then were ev ...[more]

PMID: 34832940

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Project description:Background: Dihydropteridone derivatives represent a novel class of PLK1 inhibitors, exhibiting promising anticancer activity and potential as chemotherapeutic drugs for glioblastoma. Objective: The aim of this study is to develop 2D and 3D-QSAR models to validate the anticancer activity of dihydropteridone derivatives and identify optimal structural characteristics for the design of new therapeutic agents. Methods: The Heuristic method (HM) was employed to construct a 2D-linear QSAR model, while the gene expression programming (GEP) algorithm was utilized to develop a 2D-nonlinear QSAR model. Additionally, the CoMSIA approach was introduced to investigate the impact of drug structure on activity. A total of 200 novel anti-glioma dihydropteridone compounds were designed, and their activity levels were predicted using chemical descriptors and molecular field maps. The compounds with the highest activity were subjected to molecular docking to confirm their binding affinity. Results: Within the analytical purview, the coefficient of determination (R2) for the HM linear model is elucidated at 0.6682, accompanied by an R2 cv of 0.5669 and a residual sum of squares (S2) of 0.0199. The GEP nonlinear model delineates coefficients of determination for the training and validation sets at 0.79 and 0.76, respectively. Empirical modeling outcomes underscore the preeminence of the 3D-QSAR model, succeeded by the GEP nonlinear model, whilst the HM linear model manifested suboptimal efficacy. The 3D paradigm evinced an exemplary fit, characterized by formidable Q2 (0.628) and R2 (0.928) values, complemented by an impressive F-value (12.194) and a minimized standard error of estimate (SEE) at 0.160. The most significant molecular descriptor in the 2D model, which included six descriptors, was identified as "Min exchange energy for a C-N bond" (MECN). By combining the MECN descriptor with the hydrophobic field, suggestions for the creation of novel medications were generated. This led to the identification of compound 21E.153, a novel dihydropteridone derivative, which exhibited outstanding antitumor properties and docking capabilities. Conclusion: The development of 2D and 3D-QSAR models, along with the innovative integration of contour maps and molecular descriptors, offer novel concepts and techniques for the design of glioblastoma chemotherapeutic agents.

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Dataset Information

Exploration of Benzenesulfonamide-Bearing Imidazole Derivatives Activity in Triple-Negative Breast Cancer and Melanoma 2D and 3D Cell Cultures.

Publications

Exploration of Benzenesulfonamide-Bearing Imidazole Derivatives Activity in Triple-Negative Breast Cancer and Melanoma 2D and 3D Cell Cultures.

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