Cancer is a disease that starts from the uncontrolled growth of abnormal cells in the organs or tissues of the body, which is the second leading cause of death in the world. One of the targets in discovering and developing anticancer drugs is Sirtuin-1. SIRT1 can act as a tumor suppressor or tumor promoter depending on its target in a particular signalling pathway or on particular cancer. This study aimed to study the interaction of a thiourea derivative with SIRT1 (PDB ID:4I5I) through its inhibition of histone deacetylase. Research has been carried out in silico with molecular docking (MGLTools.1.5.6) and molecular dynamics (Desmond 2019) of three thiourea derivatives to the receptor. In addition, pharmacokinetic parameters, toxicity, and selection of Lipinski's Rule of Five were also tested. Molecular docking results showed that compound b ([2-(methylcarbamothioylcarbamoyl)phenyl]benzoate) had the lowest ∆G value of −9.29 kcal/mol with a KI value of 0.156 µM compared to other thiourea derivatives and was proven by molecular dynamics tests for 30 ns and amino acids that play an active role in the interaction include the residue PheA:297. In terms of pharmacokinetics and toxicity, compound b is better than natural ligands. Compound b is predicted to be used as an anticancer candidate through further research.

Background: Prostate cancer remains a leading cause of male cancer-related mortality, largely driven by the dysregulated activation of the androgen receptor (AR) signaling pathway. The emergence of resistance, particularly in castration-resistant prostate cancer (CRPC), necessitates the discovery of innovative therapeutic approaches. This systematic review aims to consolidate contemporary evidence regarding natural products as bioactive alternatives capable of targeting the AR signaling axis. Methods: Adhering to PRISMA guidelines, a systematic search was conducted across PubMed, Scopus, and ScienceDirect databases. The review identified and qualitatively analyzed 15 original research studies that investigated the efficacy and mechanisms of various natural compounds in modulating AR signaling. Results: The analysis reveals that natural products deactivate the AR signaling axis through diverse mechanisms. Neoisoliquiritin and α-terthienyl were found to suppress AR expression, activity, and nuclear translocation. Notably, α-mangostin facilitates the degradation of the AR-V7 splice variant, a key driver of treatment resistance. Manzamine A inhibits AR biosynthesis by targeting the transcription factor E2F8. Furthermore, alternative pathways are modulated through 5-α-reductase inhibition (Annona muricata compounds) and the activation of the non-classical membrane receptor ZIP9 by (-)-epicatechin to induce apoptosis. Conclusions: The emergence of resistance, particularly in castration-resistant prostate cancer (CRPC), necessitates the exploration of innovative therapeutic approaches. This systematic review consolidates contemporary evidence regarding natural products as potential bioactive alternatives for modulating the androgen receptor (AR) signaling axis. Rather than providing a definitive clinical roadmap, this work establishes a preclinical framework for identifying substances that may deactivate the receptor, break down its resistant forms, or prevent nuclear translocation.

Context: Cancer is a disease characterized by the formation of abnormal cells and uncontrollably. Over the past three decades, cobalt complexes' anticancer potential has been thoroughly investigated, and a lot of time has been spent figuring out how they work. In another study, the 1-Benzoyl-3-methylthiourea is one of the thiourea derivatives that have anticancer activity. The Modification of thiourea into a thiourea–cobalt(III) complex was carried out to increase the anticancer activity. Aims: To obtain a thiourea-cobalt(III) derivative compound that can be used as an anticancer breast candidate through molecular docking, molecular dynamics, and predictive ADMET studies. Methods: The method used is predicting the mechanism of molecular docking inhibition using the Autodock 4.0 tool followed by molecular dynamics using Desmond. In addition, to analyze ADMET and Drug-likeness using the pkCSM online web server (https://biosig.lab.uq.edu.au/pkcsm/). Results: Of the 18 thiourea–cobalt(III) derivatives, only three compounds had a poor pharmacokinetic profile, and ten compounds did not have AMES toxicity and were not hepatotoxic. In molecular docking simulations, 16 compounds were more potent than cisplatin at the 3ERT receptor, 12 more potent at the 3PP0 receptor, and all the compounds were more potent than cisplatin at the 5NWH receptor. Molecular dynamics simulations for 50 ns were performed on the three compounds with the best binding affinity at each receptor. Conclusions: The bis-(1-(3-chlorobenzoyl)-3-methylthiourea)–cobalt(III) could be used as the best anticancer candidate through the human epidermal growth factor 2.

J. Pharm. Pharmacogn. Res., vol. 12, no. 3, pp. 423-438, May-Jun 2024. DOI: https://doi.org/10.56499/jppres23.1827_12.3.423 Original Article Synthesis and computational study of metal complex of α-mangostin as an anticancer candidate [Síntesis y estudio computacional de un complejo metálico de α-mangostin como un candidato anticancerígeno] Richa Mardianingrum1, Srie Rezeki Nur Endah1, Isti Daruwati2,3, Muchtaridi Muchtaridi3,4, Ruswanto Ruswanto5* Synthesis and computational study of metal complex of α-mangostin as an anticancer candidate

Degenerative disease is a health condition of an organ or related tissue whose condition can deteriorate over time due to changes in body cells that affect organ function as a whole. The factor is due to unhealthy life changes such as lack of activity and frequent exposure to harmful substances into the body. Degenerative diseases include hypertension, diabetes, cholesterol, cancer, and death. Harmful substances or free radicals can be inhibited by antioxidants. One drug that has antioxidant activity is ascorbic acid (Vitamin C) which functions as an immune booster and is used by the public because it is effective as an antioxidant and health therapy but there are side effects in the form of gastrointestinal. The research aimed to find candidate drug ingredients from compounds contained in black pepper seeds (Piper nigrum L.) as in silico antioxidants. The methods used are molecular docking and molecular dynamics. The results showed BLH19 had better toxicity than the comparator drug and had hydrogen interactions that could be stabilized by the amino acid Gln139. The results of molecular dynamic calculations for BLH19 have an RMSD value of 1.5 Å with a ΔGTotal of -33.50 Kcal/mol. While the comparator drug has an RMSD value of 1.6 Å with ΔGTotal -3.39 Kcal/mol. The results showed that the affinity level of ascorbic acid compared to BLH19 for the 4RP9 receptor was predicted to be a candidate for a new antioxidant drug.

Context: The development of radiopharmaceuticals derived from natural compounds has been extensively studied, particularly for cancer treatment. α-Mangostin is a molecule claimed to be toxic to cancer cells, and its derivative, an organometallic compound, has been synthesized successfully, namely bis-(α-mangostin)-cobalt(II) or AM-Co. The AM-Co structure shows promise as a radiopharmaceutical candidate, especially when labelled with radioactive iodine. Aims: To optimise the radiolabelling conditions of AM-Co with iodine-131 and assess its internalization profile in breast cancer cell lines, as well as biodistribution and pharmacokinetic profile using in vivo approaches. Methods: The radiolabelling of [131I]I-AM-Co was carried out by electrophilic aromatic substitution, with CATas the oxidising agent at low temperatures for synthesis. Internalization studies of [131I]I-AM-Co were conducted in MCF-7 cell lines. Additionally, the biodistribution and pharmacokinetic profiles were assessed by administering 0.37–1.11 MBq of [131I]I-AM-Co (i.v. route) in normal mice and rats. Results: The [131I]I-AM-Co was successfully synthesized with radiopharmaceutical purity of 99.12 ± 0.18% and internalized into MCF-7 cell lines greater than 46% after one hour of incubation. In addition, [131I]I-AM-Co demonstrates 11 times slower diffusion from blood into organs compared with iodine -131, with t½ α was 0.33 ± 0.17 hour. Interestingly, based on AUC data, it reveals that systemic exposure of [131I]I-AM-Co exhibits increasing five times than iodine-131. However, the highest accumulation of [131I]I-AM-Co was still found in the thyroid gland. Conclusions: The [131I]I-AM-Co can be synthesized, achieving a radiochemical purity of over 90%. In addition, the [131I]I-AM-Co compound greatly enhances cellular uptake and plasma concentration compared to iodine-131, which exhibits rapid clearance.