Computational Study of Bis-(1-(Benzoyl)-3-Methyl Thiourea) Platinum (II) Complex Derivatives as Anticancer Candidates.

Background: The increasing incidence of cancer every year has resulted in cancer becoming one of the most common causes of death in the world. The most common types of cancer are breast cancer, lung cancer and prostate cancer. Thiourea is one of the compounds that have anticancer effects, and its activity can be increased by structural modifications, one of which involves making a Bis-(1-(benzoyl)-3-methyl thiourea) platinum (II) metal complex. Purpose: This study aims to obtain platinum (II)-thiourea complex compounds that have a more stable interaction as an anticancer agent compared to cisplatin. Methods: The methods used are computational studies with molecular docking, simulation of molecular dynamics, and prediction of pharmacokinetics and toxicity. Results: Based on the molecular docking of the platinum (II)-thiourea complex which has the most stable interaction with lower binding energy than the native ligand and the cisplatin, namely Bis-(3-methyl-1-(naphthalene-2-carbonyl)thiourea)) Platinum (II) against breast cancer receptors (3ERT) and lung cancer (2ITO) and compounds Bis-(1-(3-chlorobenzoyl)-3-methylthiourea) Platinum (II) against prostate cancer receptors (1Z95). The evaluation results of the stability of the interaction using a 50 ns molecular dynamic simulation showed that the Bis-(1-benzoyl-3-methylthiourea) Platinum (II) which binds to the prostate cancer receptor (1Z95) has the most stable interaction. Pharmacokinetic prediction results show that the platinum (II)-thiourea complex has a good pharmacokinetic profile, but there are several compounds that are mutagenic and hepatotoxic. Conclusion: The Bis-(1-(3,4-dichlorobenzoyl)-3-methyl thiourea) platinum (II) compounds could be a suitable anticancer agent for the lungs.

Corrigendum to "Design, molecular docking, and molecular dynamics of thiourea-iron (III) metal complexes as NUDT5 inhibitors for breast cancer treatment" [Heliyon 8 (9) (2022) e10694].

[This corrects the article DOI: 10.1016/j.heliyon.2022.e10694.].

Design, molecular docking, and molecular dynamics of thiourea-iron (III) metal complexes as NUDT5 inhibitors for breast cancer treatment.

In research, anticancer agents, such as thiourea derivative compounds, and metal complexes, such as those complexed with iron (III) metal, are often studied. The metal complexes are presumably more active than thiourea derivatives as free ligands; some negative effects may be reduced. The computational studies used in this study involved molecular docking with AutoDock and molecular dynamics (MD) simulations using Desmond to evaluate the stability of the interactions. The docking and MD analysis results showed that compounds 2 and 6 had stable interactions with NUDIX hydrolase type 5 (NUDT5)-one of the therapeutic targets for breast cancer-where they had the lowest root mean square deviation (RMSD) and root mean square fluctuation (RMSF) values compared to the other compounds. Together, these compounds are anti-breast cancer drug candidates.

Synthesis, Anticancer Activity, Structure-Activity Relationship, and Molecular Modeling Studies of α-Mangostin Derivatives as hERα Inhibitor.

α-Mangostin is one of the secondary metabolites in mangosteen pericarp, which has been reported to have anti-breast cancer activity. In our previous study, three α-mangostin derivatives were computationally designed as hERα antagonists. In this present study, the designed compounds were synthesized undergoing a benzoylation reaction between α-mangostin with three benzoyl chloride derivatives to produce three derivatives, namely, AMB-1, AMB-2, and AMB-10. The synthesized compounds were then evaluated for their antiproliferative activity against the MCF-7 breast cancer cell model with hERα as the protein target. The in vitro assay shows moderate activity (57-126 µM) for all derivatives. The dynamic behaviors of all ligands, including α-mangostin and 4-hydroxytamoxifen (4-OHT), were studied with 100 ns of MD simulation. The structure-activity relationship shows that although it does not entirely concord with the expected design, it can explain the trend of α-mangostin and its derivatives antiproliferative activities against MCF-7, which associates with hERα antagonism.