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.

Context: Smallanthus sonchifolius or yacon has been reported to have hypoglycemic effects. Inhibition of sodium-glucose cotransporter 2 (SGLT-2) is one of the mechanisms of antidiabetic drugs. Aims: To evaluate potential compounds in S. sonchifolius as SGLT-2 inhibitors using molecular docking analysis and dynamic simulation, as well as predict the pharmacokinetic profiles of the potent compounds using ADMETlab 3.0. Methods: Fourteen molecules from S. sonchifolius were docked with SGLT-2 (PDB Code 7VSI) simultaneously as empagliflozin and canagliflozin as standard ligands. Three compounds, they are 3,5-dicaffeoylquinic acid (3,5-DCQA); and 3,4-dicaffeoylquinic acid (3,4-DCQA), 1-kestose, showed lower rerank scores than empagliflozin and canagliflozin. The analysis proceeded to molecular dynamic simulation by investigating the RMSD and binding energy of SGLT-2 protein in complexes with the ligands to evaluate the dynamic behavior of protein-ligand complexes. Results: All ligands illustrate similar patterns with two ligand controls, suggesting its acceptable movement from the binding site of SGLT-2. 1-Kestose exhibited stronger binding affinity with SGLT-2 during the period of simulation and continued to interact with the binding pocket of SGLT-2 until the end of the simulation, which involved some critical residues, including Phe98, Glu99, and Ser287, and mainly contributed to hydrogen bond interactions. However, 1-kestose was predicted to have low gastrointestinal absorption due to many polar substituents, while 3,4-DCQA and 3,5-DCQA have higher gastrointestinal absorption. Conclusions: One phytochemical present in S. sonchifolius is 1-kestose, which is thought to have action as an SGLT-2 inhibitor for the treatment of diabetes based on the findings of molecular docking and molecular dynamics investigations. This compound falls into BCS Class III, which means it has good solubility but poor permeability.

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: First-line therapy using artemisinin-based combination therapy (ACT) and chloroquine in cases of malaria infection has developed resistance worldwide. Aims: To synthesize functionalized dibenzylideneacetones that are similar to curcumin and to perform the in silico evaluations on Plasmodium falciparum enoyl acyl carrier protein reductase (PfENR) and through human dihydrofolate reductase (hDHFR) as targets for antimalarial agents. Methods: The functionalized dibenzylideneacetones were synthesized through a reaction of acetone with benzaldehydes in a base or acid catalyst. The resulting solids were purified by recrystallization to conduct UV/Vis, FTIR, and NMR tests. The confirmed products underwent an in silico molecular docking test on PfENR (PDB ID: 1NHG) and hDHFR (PDB ID: 1MVT). The products were obtained in good yields. Results: The confirmed products underwent in silico molecular docking test on PfENR (PDB ID: 1NHG) and hDHFR (PDB ID: 1MVT). The products were obtained with good yields. Based on in silico results, the dibenzylideneacetone was predicted to have a strong potential to inhibit the growth of malaria parasites through inhibit malaria growth through the PfENR pathway more than through the hDHFR pathway because its moldock score was lower than its native ligand. Conclusions: This study showed a promising pathway to obtain antimalarial agents for further application in the medical and pharmaceutical industries.

Rheumatoid arthritis (RA) is a progressive and chronic systemic autoimmune disease. However, currently treatment is often carried out using NSAIDs and corticosteroids. Although it reduces symptoms, this treatment has a high rate of side effects. This study aims to determine the anti-inflammatory property of Curcuma heyneana so that it can be used as an alternative treatment for RA. Based on author knowledge, this study on C. heyneana from the Indonesian region for the treatment of RA is still limited. C. heyneana’s rhizome was extracted by maceration with ethanol followed by fractionation process using n-hexane, ethyl acetate, and n-butanol. The anti-inflammatory invitro activities were determined by heat-induced hemolysis, effect on protein denaturation, and cyclooxygenases (COX) inhibition assay. Molecular docking of major predictive compounds was performed by AutoDock Vina. The results showed that some fractions of C. heyneana contained terpenoids, flavonoids, and alkaloids. The ethyl acetate fraction exhibited the highest anti-inflammatory activity, which was attributed to the presence of curcuminoids. Molecular docking studies further confirmed the potential of demethoxycurcumin, a curcuminoid identified in the ethyl acetate fraction, to inhibit COX-2. These findings suggest that C. heyneana, particularly its previously unreported curcuminoid-rich fractions, holds promise as a natural anti-inflammatory agent. Further research is warranted to explore the therapeutic potential of this plant in the management of RA and other inflammatory disorders.

J. Pharm. Pharmacogn. Res., vol. 11, no. 6, pp. 1123-1136, Nov-Dec 2023. DOI: https://doi.org/10.56499/jppres23.1718_11.6.1123 Original Article QSAR study of benzylidene hydrazine benzamides derivatives with in vitro anticancer activity against human lung cancer cell line A459 [Estudio QSAR de derivados de benzilideno hidrazina benzamidas con actividad anticancerígena in vitro frente a la línea celular de cáncer de QSAR study of benzylidene hydrazine benzamides derivatives with in vitro anticancer activity against human lung cancer cell line A459