Antibiotic and antifungal resistance problems have been prevalent in recent decades. One of the efforts to solve the problems is to develop new medicines with more potent antibacterial and antifungal activity. N-phenylbenzamides have the potential to be developed as antibacterial and antifungal medicine. This study aimed to synthesize N-phenylbenzamides and evaluate their in silico and in vitro antibacterial and antifungal activities. The in silico studies conducted absorption, distribution, metabolism, excretion and toxicity (ADMET) predictions along with molecular docking studies. ADMET predictions used pkCSM software online, while the docking studies used MVD software (Molegro ^® Virtual Docker version 5.5) on Aminoglycosid-2 ″-phosphotransferase-IIa (APH2 ″-IIa) enzyme with protein data bank (PDB) ID code 3HAV as antibacterial and aspartic proteinases enzyme (Saps) with PDB ID code 2QZX as an antifungal. In vitro, antibacterial and antifungal tests were carried out using the zone of inhibition (ZOI) method. The five N-phenylbenzamides (3a–e) were successfully synthesized with a high yield. Based on in silico and in vitro studies, compounds 3a–e have antibacterial and antifungal activities, where they can inhibit the growth of Gram-positive bacteria (Staphylococcus aureus), Gram-negative (Escherichia coli), and Candida albicans. Therefore, compounds 3a–e can be developed as a topical antibacterial and antifungal agent.

Curcumin derivatives (Curcuminoids) are a highly intriguing class of phytochemical compounds, widely discussed due to their presence as active ingredients in various pharmaceutical formulations and food supplements. There are three main compounds in curcuminoids: curcumin, desmethoxycurcumin, and bisdemethoxycurcumin. These compounds exhibit distinct chemical structures, which significantly influence their chemical and physical properties, pharmacokinetic profiles, and pharmacodynamic characteristics. From a pharmacokinetic perspective, curcuminoid-based formulations present unique challenges due to their poor water solubility and low permeability in the gastrointestinal tract (GIT). In terms of pharmacodynamics, curcuminoids interact with multiple receptor targets and enzymes, contributing to a wide range of pharmacological effects, including anti-inflammatory, antioxidant, and anticancer activities, among others. Therefore, this book explores in depth the chemical and physical properties of curcumin derivatives and their impact on pharmacokinetic and pharmacodynamic profiles.

Context: N-(4-t-butylbenzoyl)-N’-phenylthiourea, a derivative compound of N-benzoyl-N’-phenylthiourea, has relatively high lipophilicity with the epidermal growth factor receptor and silent mating type information regulation-1 enzyme as its molecular targets. Aims: To determine the anticancer activity of N-(4-t-butylbenzoyl)-N’-phenylthiourea as an in silico and in vitro anticancer candidate for the breast and cervical cancer. Methods: In silico test was performed to predict the cytotoxic activity using AutoDock Vina. This activity was also measured in vitro using the Microculture Tetrazolium Technique assays of three cancer cells (MCF-7, T47D, and HeLa) and normal cells (Vero cells). Results: In silico test predicted that N-(4-t-butylbenzoyl)-N’-phenylthiourea was more cytotoxic at epidermal growth factor receptor than silent mating type information regulation-1 receptor. In vitro tests showed it exhibited cytotoxic activities against MCF-7, T47D, and HeLa without harming Vero cells. Conclusions: N-(4-t-butylbenzoyl)-N’-phenylthiourea has the potential as an anticancer candidate for breast and cervical cancers.

The increasing number of cancer patients and the challenge of multidrug resistance (MDR) demand more effective drugs, which can be developed by modifying compounds derived from natural resources, such as the flavonoid-rich temu kunci rhizome (Boesenbergia pandurata (Roxb.) Schlecht.). This study aims to predict the cytotoxicity and toxicity of 20 Pinostrobin derivatives and 19 Chalcone derivatives as potential anticancer candidates. Estrogen receptor alpha (ER-α), a validated cancer therapy target, was used for molecular docking in in silico tests using Molecular Graphics Laboratory (MGL) Tools (including, AutoDock Vina, AutoDock Tools 4.1, and Python 2.5.2) and PyRx Program. Toxicity was predicted using the pkCSM program and Protox online tool. The docking process involved binding the compounds to ER-α (PDB IDs 6CHZ and 3ERT), with the binding energy indicating activity; lower binding energy values suggest greater cytotoxic potential and stronger ligand-receptor interactions. The results showed that Chalcone derivatives from temu kunci exhibited lower toxicity and higher cytotoxic activity compared to Pinostrobin derivatives and the reference compound, Tamoxifen (TAM). Notably, Bis-3-chlorobenzyloxychalcone and Bis-2-chlorobenzyloxychalcone demonstrated the highest predicted cytotoxic activity. In conclusion, Chalcone derivatives are promising candidates for further development as more effective anticancer drugs, especially those that outperform Tamoxifen. These findings highlight the potential of natural compounds, particularly Chalcone derivatives, in combating cancer while addressing the growing challenge of MDR in clinical treatments.

Context: The chalcone derivative compounds (bis-2-chlorobenzyloxychalcone and bis-3-chlorobenzyloxychalcone) synthesized from pinostrobin, which is found in Boesenbergia rotunda (L.) Mansf., which has cytotoxic activity relative to the estrogen receptor alpha. Aims: To determine the anticancer activity of chalcone derivative compounds synthesized from B. rotunda as an in silico and in vitro breast cancer candidate. Methods: An in silico test was performed to predict the cytotoxic activity using AutoDockVina and the synthesis of chalcone and derivatives from pinostrobin compounds contained in B. rotunda using the green synthesis method through Williamson etherification reaction and phase-transfer catalyst (PTC)-assisted microwave irradiation. This activity was also tested in vitro using the microculture tetrazolium technique (MTT) assay of breast cancer cells (MCF-7) and normal cells (Vero cells). Results: In silico tests predicted that chalcone derivatives were more cytotoxic at estrogen receptor alpha than lead compounds (pinostrobin and chalcone compound). In vitro tests showed that the bis-2-chlorobenzyloxychalcone compound showed an IC50 greater than 100 μg/mL, which indicated it was not active, and the bis-3-chlorobenzyloxychalcone compound exhibited an IC50 less than 100 μg/mL, which indicated it was moderately active. Thus, in vitro tests showed that two compounds were less potent against MCF-7 cells than the reference compound (tamoxifen). However, it was selective against MCF-7 breast cancer cells while not harming Vero cells. Conclusions: The bis-2-chlorobenzyloxychalcone and bis-3-chlorobenzyloxychalcone compounds identified in B. rotunda exhibited a favorable selectivity index, suggesting moderate potential as anticancer candidates for breast cancer. However, further research and development are required to validate their efficacy and safety.

Women worldwide, including in Indonesia, are particularly vulnerable to breast cancer, which is often detected at advanced stages. Existing treatment approaches have weaknesses and low success rates, as the drugs used become less effective and cancer cells can develop resistance. Therefore, we need to innovate to create new anticancer drug candidates from natural sources like the fingerroot rhizome (Boesenbergia rotunda). In this study, in silico testing was conducted to predict cytotoxic activity using AutoDock Vina. The isolation of the rhizome and the synthesis of chalcone derivatives were performed using green synthesis methods through Williamson ether reactions with microwave irradiation. Structure identification was carried out using an IR spectrometer and a 1H-NMR spectrometer. In vitro activity was assessed using MTT assays on MCF-7 cells and normal Vero cells. The results showed that the chalcone compounds, Bis-4-chlorobenzyloxychalcone and Bis-4-bromobenzyloxychalcone, exhibited better bioavailability, toxicity, and activity in silico. In vitro, they demonstrated significant cytotoxic activity compared to tamoxifen against MCF-7 cells and greater selectivity towards MCF-7 cells compared to normal Vero cells. Therefore, Bis-4-chlorobenzyloxychalcone and Bis-4-bromobenzyloxychalcone have the potential to be candidates for anticancer drugs for breast cancer, providing alternative options to reduce the side effects associated with drug use.