Aldol derivatives of Thioxoimidazolidinones as potential anti-prostate cancer agents

Khatik, Gopal L.; Kaur, Jasmine; Tikoo, Kulbhushan; Venugopalan, P.; Nair, Vipin A.

doi:10.1016/j.ejmech.2011.04.050

Cited by 27 publications

(14 citation statements)

References 41 publications

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“…Figures 3 and 4 show dose-dependent curves of the conjugates 6 and 15 on viability of LNCaP and PC-3 cells compared with bicalutamide and flutamide in RPMI-1640 medium supplemented in 10% FBS, slightly modified from literature reported methods. 41-42 Both conjugates demonstrate more potent antiproliferation effect than the tested antiandrogens.…”

Section: Resultsmentioning

confidence: 99%

Antitumor agents 290. Design, synthesis, and biological evaluation of new LNCaP and PC-3 cytotoxic curcumin analogs conjugated with anti-androgens

Shi

Wada

Ohkoshi

et al. 2012

Bioorganic & Medicinal Chemistry

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In our continuing study of curcumin analogs as potential anti-prostate cancer drug candidates, 15 new curcumin analogs were designed, synthesized and evaluated for cytotoxicity against two human prostate cancer cell lines, androgen-dependent LNCaP and androgen-independent PC-3. Twelve analogs (5-12, 15, 16, 19, and 20) are conjugates of curcumin (1) or methyl curcumin (2) with a flutamide- or bicalutamide-like moiety. Two compounds (22 and 23) are C4-mono- and difluoro-substituted analogs of dimethyl curcumin (DMC, 21). Among the newly synthesized conjugates compound 15, a conjugate of 2 with a partial bicalutamide moiety, was more potent than bicalutamide alone and essentially equipotent with 1 and 2 against both prostate tumor cell lines with IC50 values of 41.8 μM (for LNCaP) and 39.1 μM (for PC-3). A cell morphology study revealed that the cytotoxicity of curcumin analogs or curcumin-antiandrogen conjugates detected from both prostate cancer cell lines might be due to the suppression of pseudopodia formation. A molecular intrinsic fluorescence experiment showed that 1 accumulated mainly in the nuclei, while conjugate 6 was distributed in the cytosol. At the tested conditions, antiandrogens suppressed pseudopodia formation in PC-3 cells, but not in LNCaP cells. The evidence suggests that distinguishable target proteins are involved, resulting in the different outcomes toward pseudopodia suppression.

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Section: Resultsmentioning

confidence: 99%

Antitumor agents 290. Design, synthesis, and biological evaluation of new LNCaP and PC-3 cytotoxic curcumin analogs conjugated with anti-androgens

Shi

Wada

Ohkoshi

et al. 2012

Bioorganic & Medicinal Chemistry

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“…The molecules were selected from the available literature having a different class of compounds, that is, bicalutamide [21], propionamides [22], and thioxoimidazolidinones [23] as shown in Fig. 1.…”

Section: Resultsmentioning

confidence: 99%

A Comparative Study of Stereochemical Effects of Anti-Prostate Agents by Molecular Docking

Osanyinpeju

Bashary

Mittal

et al. 2018

Asian J Pharm Clin Res

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Objective: A comparative study of anti-prostate agents to investigate the stereochemical influences on binding affinity by molecular docking. Methods:Structures of enantiomers (R and S stereoisomers) for known anti-prostate cancer (PCa) agents were drawn using ChemBioDraw 2D software. Thereafter, they were converted to 3D structures using the ChemBioDraw 3D software in which they were subjected to energy minimization using the MM2 method and then saved as PDB extension files which can be accessed using the ADT interface. AutoDock Vina (ADT) 1.5.6 software version was used for molecular docking study.Results: A total of 12 different anti-PCa agents were selected and drawn including well-known drug R-bicalutamide. All molecules showed the binding affinity with respect to the nature of stereochemistry. R-stereoisomers showed better interaction as well as binding affinity toward 1z95 (mutated androgen receptor protein involved in the progression of PCa) whereas their S-stereoisomers were found inferior in comparison. Conclusion:This study showed that CB1-R and R-bicalutamide (with R-stereochemistry) were better in binding affinity comparative to their counterpart CB1-S and S-Bicalutamide (with S-stereochemistry). All the selected anti-PCa agents were showing the effect of stereochemical center; therefore, we must choose the right kind of stereochemistry while planning to develop the newer anti-PCa agents.

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“…Thiohydantoins are sulfur analogs of hydantoins with one or two carbonyl groups that have been substituted by thiocarbonyl groups [19]. 2-Thioxoimidazolidin-4-ones are very useful synthetic intermediates and have found a myriad of applications in the area of therapeutics [20,21]. Hence, 2-thiohydantoins were used as reference standards for the development of C-terminal protein sequencing [22], reagents for dying development [23], the complexation of metal cations in textile printing, and polymerization catalysis [24,25].…”

Section: Introductionmentioning

confidence: 99%

Synthesis of novel 2-thioxo-4-imidazolidinone derivatives and evaluation of their antibacterial, and antifungal activities

2021

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The infectious diseases caused by antimicrobials pathogens are difficult, harmful, and sometimes impossible to treat. Therefore, design new drugs to treat antimicrobial infections is the biggest challenge for modern medicine. 2-Thioxo-4-imidazolidinone is used for the synthesis of a wide variety of new substituted imidazolidinone derivatives. In this study, we designing eight novel compounds derived for the 2-thioxo-4-imidazolidinones (5ah). The preparation was in two steps via Micheal addition of phenyl hydrazide (2a), 4-methyl phenyl hydrazide 2b on N-substituted maleimides 1a-d in ethanol, and the second step by reaction of maleimide derivatives with cyclohexyl isothiocyanate 4 in acetonitrile. The chemical structures of the compounds were identified using FT-IR, 1 H-NMR, 13 C-NMR, and mass spectra, as well as the melting point. The antibacterial and antifungal evaluation was carried out to target their activities. Compound N-(5-(2-((4-chlorophenyl)amino)-2-oxoethyl)-3cyclohexyl-4-oxo-2-thioxoimidazolidin-1-yl) benzamide (5b) exhibited antibacterial activity toward Staphylococcus aureus and Pseudomonas aeruginosa with equal minimum inhibitory concentration (MIC) values of 25 mg/mL. Compounds N-(3-cyclohexyl-4-oxo-5-(2-oxo-2-(phenylamino)ethyl)-2-thioxoimidazolidin-1-yl) benzamide (5a), N-(5-(2-((4-chlorophenyl)amino)-2-oxoethyl)-3-cyclohexyl-4-oxo-2-thioxoimidazolidin-1-yl) benzamide (5b), N-(5-(2-((4-bromophenyl)amino)-2-oxoethyl)-3-cyclohexyl-4-oxo-2-thioxo imidazolidin-1-yl) benzamide (5c), and N-(3-cyclohexyl-4-oxo-5-(2-oxo-2-(phenylamino)ethyl)-2-thioxoimidazolidin-1-yl)-4methyl benzamide (5e) exhibited antifungal activity toward Candida albicans, while all compounds exhibited antifungal activity toward Aspergillus niger except for compound 5h, with various MIC values. In conclusion, the results demonstrate that the new compounds have to promise as antifungal agents. Moreover, compound 5b could develop as an antibacterial agent.

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Aldol derivatives of Thioxoimidazolidinones as potential anti-prostate cancer agents

Cited by 27 publications

References 41 publications

Antitumor agents 290. Design, synthesis, and biological evaluation of new LNCaP and PC-3 cytotoxic curcumin analogs conjugated with anti-androgens

Antitumor agents 290. Design, synthesis, and biological evaluation of new LNCaP and PC-3 cytotoxic curcumin analogs conjugated with anti-androgens

A Comparative Study of Stereochemical Effects of Anti-Prostate Agents by Molecular Docking

Synthesis of novel 2-thioxo-4-imidazolidinone derivatives and evaluation of their antibacterial, and antifungal activities

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