A Simple and Efficient Approach to the Synthesis of 4-Aryl-2-dialkylphosphonomethyl-4-oxobutanenitrile

Progesterone receptor (PR) agonists represent pivotal agents in trapping breast cancer cells through modulating the expression of estrogen receptor (ER). The present investigation aimed to test three novel thiadiazolecontaining compounds as antibreast cancer agents. Test compounds were synthesized and abbreviated as 2-{(5-amino-1, 3, 4-thiazole-2-yl) amino}-4-(4-chloro-3methylphenyl)-4-oxobutanoic acid (TAB), 4-(4-chloro-3methylphenyl)-4-oxo 2-[(5-sulfanyl-1, 3, 4-thiadiazol-2-yl)] sulfanyl-butanoic acid (TSB) and 4-(4-chloro-3methylphenyl)-4-oxo 2-[(5-sulfanyl-1, 3, 4-thiadiazol-2-yl)] sulphonyl-botanic acid (TSSB). Molecular docking of the test compounds with PR was simulated. The IC 50 of the test compounds against both Michigan cancer foundation-7 (MCF-7) and HepG2 was determined. Ehrlich solid tumor (EST) was grown in the right thigh of the mouse as a model of breast cancer in vivo. Hepatic and renal functions, besides hematological indicators, were tested. The expression of ER and ER genes in EST was determined using real-time PCR. Immunohistochemistry was carried out for the determination of Ki-67 and cyclindependent kinase 1 (CDK-1) in EST. Our results revealed that TAB, TSB and TSSB reduced Ehrlich tumor size by 48, 64 and 52%, respectively, compared to the EST control group. The docking scores achieved by TAB, TSB and TSSB with PR were −9.29, −9.41 and −9.24 kcal/mol, respectively. The most potent compound against MCF-7 was TSB, with an IC 50 of 3.9 g/ml. The administration of test compounds suppressed Ki-67 and CDK1, and the best effect was observed at TSB. Our findings suggest that test compounds are applicants to be antibreast cancer agents.

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Computational and Molecular Docking Studies of New Benzene Sulfonamide Drugs with Anticancer and Antioxidant Effects

Mohamed

Abdelgawad

Hegab

et al. 2023

COS

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The studies on the potential usage of benzene sulfonamide derivatives as anticancer agents are limited. Thus, in this study, a series of new sulfonamide drugs are synthesized by reacting aldehydes thio-semi-carbazones derivatives with benzene sulphonyl chloride to form benzylidene-N-(phenylsulfonyl) hydrazine-1-carbothioamide derivatives. Spectral techniques, such as Fourier-transform infrared analysis (FT-IR), proton nuclear magnetic resonance (1HNMR) and mass spectroscopy, are used to characterize the newly synthesized compounds. The two derivatives, 2-(4-methoxy benzylidene)-N-(phenylsulfonyl) hydrazine-1-carbothioamide (4c) and 2-(4-dimethylamino) benzylidene)-N-(phenylsulfonyl) hydrazine-1-carbothioamide (4e), show the most potent anticancer effects against MCF-7 breast carcinoma cell lines. Meanwhile, these two derivatives show the lowest antioxidant activities. To study the anti-breast cancer activity of the newly synthesized compounds, a molecular docking study is used to analyze the binding energy for the nonbonding interactions between the ligands (studied compounds) and receptor (4PYP (pdb code: 4FA2)) against human breast cancer (MCF-7) cells. The bioavailability of all studied compounds is confirmed by pharmacological investigations using Mol inspiration and absorption, distribution, metabolism, excretion, and toxicity online servers.

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A Simple and Efficient Approach to the Synthesis of 4-Aryl-2-dialkylphosphonomethyl-4-oxobutanenitrile

Cited by 3 publications

References 25 publications

An efficient one-pot synthesis of benzofurans from functionalized tetrahydronaphtalenes

An efficient one-pot synthesis of benzofurans from functionalized tetrahydronaphtalenes

Synthesis and evaluation of novel thiazole moiety-containing compounds as antibreast cancer agents

Computational and Molecular Docking Studies of New Benzene Sulfonamide Drugs with Anticancer and Antioxidant Effects

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