Synthesis, Antitumor Evaluation, Molecular Modeling and Quantitative Structure–Activity Relationship (QSAR) of Novel 2-[(4-Amino-6-N-substituted-1,3,5-triazin-2-yl)methylthio]-4-chloro-5-methyl-N-(1H-benzo[d]imidazol-2(3H)-ylidene)Benzenesulfonamides

Department of Biotechnology, Intercollegiate Faculty of Biotechnology, University of Gdańsk and Medical University of Gdańsk, ul. Abrahama 58, 80-307 Gdansk, Poland

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Int. J. Mol. Sci. 2020, 21(8), 2924; https://doi.org/10.3390/ijms21082924

Received: 19 March 2020 / Revised: 16 April 2020 / Accepted: 20 April 2020 / Published: 22 April 2020

(This article belongs to the Section Biochemistry)

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Abstract

A series of novel 2-[(4-amino-6-R²-1,3,5-triazin-2-yl)methylthio]-4-chloro-5-methyl-N-(5-R¹-1H-benzo[d]imidazol-2(3H)-ylidene)benzenesulfonamides 6–49 was synthesized by the reaction of 5-substituted ethyl 2-{5-R¹-2-[N-(5-chloro-1H-benzo[d]imidazol-2(3H)-ylidene)sulfamoyl]-4-methylphenylthio}acetate with appropriate biguanide hydrochlorides. The most active compounds, 22 and 46, showed significant cytotoxic activity and selectivity against colon (HCT-116), breast (MCF-7) and cervical cancer (HeLa) cell lines (IC₅₀: 7–11 µM; 15–24 µM and 11–18 µM), respectively. Further QSAR (Quantitative Structure–Activity Relationships) studies on the cytotoxic activity of investigated compounds toward HCT-116, MCF-7 and HeLa were performed by using different topological (2D) and conformational (3D) molecular descriptors based on the stepwise multiple linear regression technique (MLR). The QSAR studies allowed us to make three statistically significant and predictive models for them. Moreover, the molecular docking studies were carried out to evaluate the possible binding mode of the most active compounds, 22 and 46, within the active site of the MDM2 protein. View Full-Text

Keywords: benzenesulfonamide; synthesis; 1,3,5-triazines; cytotoxicity; QSAR; molecular docking

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Tomorowicz, Ł.; Sławiński, J.; Żołnowska, B.; Szafrański, K.; Kawiak, A. Synthesis, Antitumor Evaluation, Molecular Modeling and Quantitative Structure–Activity Relationship (QSAR) of Novel 2-[(4-Amino-6-N-substituted-1,3,5-triazin-2-yl)methylthio]-4-chloro-5-methyl-N-(1H-benzo[d]imidazol-2(3H)-ylidene)Benzenesulfonamides. Int. J. Mol. Sci. 2020, 21, 2924. https://doi.org/10.3390/ijms21082924

AMA Style

Tomorowicz Ł, Sławiński J, Żołnowska B, Szafrański K, Kawiak A. Synthesis, Antitumor Evaluation, Molecular Modeling and Quantitative Structure–Activity Relationship (QSAR) of Novel 2-[(4-Amino-6-N-substituted-1,3,5-triazin-2-yl)methylthio]-4-chloro-5-methyl-N-(1H-benzo[d]imidazol-2(3H)-ylidene)Benzenesulfonamides. International Journal of Molecular Sciences. 2020; 21(8):2924. https://doi.org/10.3390/ijms21082924

Chicago/Turabian Style

Tomorowicz, Łukasz, Jarosław Sławiński, Beata Żołnowska, Krzysztof Szafrański, and Anna Kawiak. 2020. "Synthesis, Antitumor Evaluation, Molecular Modeling and Quantitative Structure–Activity Relationship (QSAR) of Novel 2-[(4-Amino-6-N-substituted-1,3,5-triazin-2-yl)methylthio]-4-chloro-5-methyl-N-(1H-benzo[d]imidazol-2(3H)-ylidene)Benzenesulfonamides" International Journal of Molecular Sciences 21, no. 8: 2924. https://doi.org/10.3390/ijms21082924

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Synthesis, Antitumor Evaluation, Molecular Modeling and Quantitative Structure–Activity Relationship (QSAR) of Novel 2-[(4-Amino-6-N-substituted-1,3,5-triazin-2-yl)methylthio]-4-chloro-5-methyl-N-(1H-benzo[d]imidazol-2(3H)-ylidene)Benzenesulfonamides

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