Current Drug Discovery Technologies - Volume 22, Issue 6, 2025

After COVID-19, tuberculosis remained the world's second most infectious fatal disease in 2022, with about 410 million people developing MDR TB, according to WHO. The fast increase of MDR and XDR-TB has posed a significant clinical problem in tuberculosis treatment. Bedaquiline, the first FDA-approved medicine for MDR-TB treatment, has caused cardiotoxicity and hepatotoxicity due to high lipophilicity or hERG potassium channel blockage throughout the last four decades. To overcome medication resistance and toxicity, there is an urgent need to create innovative drugs with improved efficacy against specific enzymes.

The work focused on the biological importance of the Quinazoline pharmacophore scaffold, and it involved the virtual screening and development of 180 novel Quinazoline derivatives in order to find potential hit candidates against molecular dual targets (Pks-13 esterase and DNA gyrase). Based on docking scores lower than (-7.5, -7.6 kcal/mol) of the standard compound, 80 drug molecules were screened using AUTODOCK Vina and filtered by ADMET profile. The top five HIT compounds developed with good binding interactions, acceptable ADME features that obeys the Lipinski Rule of Five, and no toxicity produced as compared to standard bedaquiline were chosen.

Docking scores showed that compound RBSI64 had a substantial binding affinity against dual targets (-11.6, -8.2 kcal/mol) than Bedaquiline (-7.5, -7.6 kcal/mol). MD simulation at 100 ns was carried out to investigate the protein's dynamic behaviour with the standard and ligand complex.

The results indicated that RBSI64 could be a useful template for developing MDR and XDR-TB inhibitors. The current study contributes to the identification of promising antitubercular candidates against targeted enzymes.

Cardiovascular disease continues to be a major global health challenge, characterized by high rates of mortality and morbidity. Medicinal plants, rich in bioactive compounds, offer potential avenues for reducing the incidence of cardiovascular disease.

The objective of this research was to evaluate the efficacy of Thymus atlanticus (T. atlanticus) aqueous extract in preventing hyperlipidemia induced by a high-fat, high-sucrose diet (HFSD) in a rat model.

Male Wistar rats were divided into three groups (n=5). The first group (normal control group) received a normal basal diet. The second group (HFSD group) received a HFSD containing a normal diet (68.5%), fat (15%), cholesterol (1.5%), and sucrose (15%). The third group (HFSD treated with thyme extract) received the HFSD and was administered orally with T. atlanticus extract (500 mg/kg bw). After 8 weeks, blood and liver samples were taken for biochemical analysis.

The results showed that HFSD intake elevated plasmatic lipids, blood fasting glucose, hepatic biochemical parameters, and inflammation. Moreover, HFSD resulted in increased liver weight, hepatic lipids, and oxidative stress. However, the treatment with T. atlanticus extract attenuated the altered parameters by lowering or restoring the levels of plasmatic lipids (TGs: -12.21%; LDL-C: -21.49%), glycated hemoglobin (-23.33%), hepatic parameters (AST: -25.04%; ALT: -10.42%; ALP: -42.81%), and inflammation. Additionally, thyme extract reduced the levels of hepatic lipids (TGs: -21.13%; TC: -12.77%) and ameliorated hepatic oxidative status by reducing malondialdehyde levels (-10.87%) and enhancing the antioxidant effect (+25.71%) of hepatic extract.

We conclude that the traditionally used aqueous extract of T. atlanticus protected against the detrimental effects of HFSD intake, and its supplementation would be an effective strategy to protect the liver and cardiovascular system. While promising, these benefits need to be validated through clinical trials.

Telomerase is a well-recognised and a promising target for cancer therapy. In this study, we selected ligand-based approaches to design telomerase inhibitors for the development of potent anticancer agents for future cancer therapy.

To investigate the chemical characteristics required for telomerase inhibitory activity, a ligand-based pharmacophore model of oxadiazole derivatives reported from the available literature was generated using the Schrodinger phase tool. This selected pharmacophore hypothesis is validated by screening a dataset of reported oxadiazole derivatives. The pharmacophore model was selected for virtual screening using ZINCPharmer against the ZINC database. The ZINC database molecules with pharmacophore features similar to the selected pharmacophore model and good fitness score were taken for molecular docking studies. With the pkCSM and SwissADME tools we predicted the pharmacokinetic and toxicity of top ten ZINC database compounds based on docking score, binding interactions and identified two in-silico potential compounds with good absorption, distribution, metabolism, and less toxicity. Then both the hit molecules were exposed to molecular dynamic simulation integrated with MM-PBSA binding free energy calculations using GROMACS tools.

The generated pharmacophore model displayed five features, two hydrophobic and three aromatic rings. The MM-PBSA calculations exhibited that the free binding energy of selected protein-ligand complexes were found stable and stabilized with non-polar and van-der walls free energies.

Our study suggests that ZINC82107047 and ZINC8839196 can be used as hit molecules for future biological screening and for discovery of safe and potent drugs as telomerase inhibitors for cancer therapy.

Angina pectoris, a common cardiovascular condition, necessitates the development of effective therapeutic agents. Nisoldipine, a calcium channel blocker, and its analogues have shown potential in treating this condition. However, the optimization of these compounds for enhanced therapeutic efficacy remains a critical challenge.

This study aimed to investigate the therapeutic potential of Nisoldipine analogues through in silico analysis, with the goal of identifying lead compounds for the treatment of angina pectoris and optimizing their formulation for improved solubility and drug release.

Eighteen Nisoldipine derivatives were screened using in silico techniques, including molecular docking, SWISS ADME analysis, and molecular dynamics (MD) simulations. The top candidate, ZINC26826387, was identified and further analyzed. A comprehensive gene set analysis was performed using OMIM, GeneCards, and STITCH databases to identify target hub genes associated with angina pectoris. PPI network analysis and CytoHubba ranking were used to prioritize key genes for further study. Additionally, the lead compound was optimized through nanoparticle formulation, and the resulting nanoparticle tablets were characterized for solubility, dissolution, particle size, entrapment efficiency, and zeta potential. ANOVA was used to analyze the characterization data.

ZINC26826387 emerged as the most promising Nisoldipine analogue, exhibiting superior solubility, absence of AMES toxicity, strong molecular docking interaction with the target protein (docking score of -8.0 kcal/mol), and favourable pharmacokinetic properties. MD simulation confirmed the stability of the ligand-receptor complex. The study also identified 88 target hub genes associated with angina pectoris, with PTGS2 prioritized as a key gene. The nanoparticle formulation of ZINC26826387 significantly enhanced solubility by 2.53-fold compared to the unformulated compound. The optimized nanoparticle tablets achieved a 98.53% drug release within 30 minutes, with an average particle size of 50 nm, entrapment efficiency of 98.89%, and zeta potential of -52 mV, indicating good stability and uniformity.

The study demonstrates the therapeutic potential of ZINC26826387, a Nisoldipine analogue, through its enhanced solubility and reduced crystallinity. The lead compound was made into Nanoparticles using Pluronic F407 as carrier. These nanoparticles were further formulated to oral disintegrating tablets for rapid drug release, good stability compared to conventional tablets. These findings suggest that ZINC26826387 could be a promising candidate for the treatment of angina pectoris.

Cannabigerol (CBG), being one of the non-psychotropic phyto-cannabinoid, has been labelled and recognized to be antioxidant and neuroprotective; it may conceivably hold depression-relieving activity. Consequently, the objective of the present research procedure was to explore the depression-alleviating competence of cannabigerol in both stressed and unstressed mice using computational/in-silico modelling, followed by in-vivo analysis.

Target genes for Major Depressive Disorder (MDD) were identified using GeneCards and Swiss Target Prediction, with common targets screened via Venny software. STRING database analysis established protein-protein interactions (PPI), identifying CNR2 (CB2 receptor) as a key target. Molecular docking of CBG with CB2 (PDB ID: 8GUR) showed strong binding, prompting in-vivo evaluation. ADME profiling via Schrödinger Maestro v10.5 confirmed CBG’s high oral absorption and favorable pharmacokinetics. Male Swiss albino mice underwent chronic unpredictable mild stress (CUMS) for three successive weeks, with CBG (10, 20, 40 mg/kg) and imipramine (15 mg/kg) administered and various behavioral and biochemical parameters being analyzed.

Cannabigerol demonstrated maximum oral absorption in ADME predictions using Schrödinger's Maestro (v10.5). Wayne diagram illustrated MDD-related targets, with CB2 (CNR2) rankings in top targets, based on SwissADME and Venny software analysis. Docking analysis revealed a high binding affinity (-10.53) for CB2, outperforming cannabidiol (-9.56) and comparable to Δ9-THC (-10.11). During in-vivo evaluation, CBG (40 mg/kg) and Imipramine 15 mg/kg significantly reduced CUMS-induced exalted plasma corticosterone, nitrite quantities, and monoamine oxidase-A action in the brain of stressed mice. Additionally, both treatments substantially reversed the unpredictable chronic stress-induced decline in catalase action, demonstrating CBG’s possible potential in alleviating depression-like symptoms in mice.

Cannabigerol has shown significant depressive alleviating potential in mice exposed to chronic and unpredictable stress regimes, possibly via interaction with cannabinoid receptors as indicated by in-silico modelling, which has been validated by our findings of the in-vivo protocol.

Vitamin D plays a crucial role in maintaining muscle and bone health and has been increasingly implicated in neurological disorders, including depression and anxiety, which are conditions closely associated with dysregulation of the serotonin 1A receptor (5-HT1A receptor). This study employs molecular modeling techniques to investigate the potential agonistic activity of Vitamin D on the 5-HT1A receptor. Additionally, it seeks to elucidate the key structural motifs and molecular interactions that underline the binding affinity between Vitamin D and the receptor. The insights gained from this research may inform the design of Vitamin D-derived compounds with optimized pharmacological profiles, contributing to therapeutic advancements in related neurological conditions.

We selected five structures of the 5-HT1A receptor (PDB IDs: 7E2Y, 7E2Z, 8W8B, 8JSP, and 8JT6) for Protein-Ligand Interaction Fingerprint (PLIF) analysis. We conducted molecular docking to evaluate the binding efficiency of two forms of Vitamin D, ergocalciferol and cholecalciferol, to the 5-HT1A receptor. Following this, we performed Molecular Dynamics (MD) simulations to assess the stability of these interactions.

Docking results revealed binding energies below -6.64 kcal/mol for both forms of Vitamin D, with ergocalciferol achieving a maximum binding energy of -7.78 kcal/mol. ASP116 emerged as a pivotal residue in stabilizing these interactions. MD simulations indicated that the Vitamin D-5-HT1A complexes exhibited stability comparable to the serotonin-bound 5-HT1A receptor complex.

Our study suggests that Vitamin D may function as an agonist for the 5-HT1A receptor, with ASP116 playing a critical role in binding. Yet, further in vitro and in vivo studies are necessary to validate these findings and explore the therapeutic potential of Vitamin D-derived compounds.

Superfoods' nutritional characteristics and health benefits have garnered attention recently. These foods contain vitamins, minerals, flavonoids, and polyphenols, which prevent disease and promote health. This review examines the nutritional and therapeutic properties of amla, maca, jackfruit, Brazil nuts, and goji berries. Recent study highlights their role to mitigate chronic diseases like diabetes, heart disease, dementia, and cancer.

This extensive review aims to cover the health and nutritional benefits of su-perfoods. It also discusses the macro- and micronutrients of amla, maca, jackfruit, Brazil nuts, and goji berries. Additionally, we explore the potential of superfoods to protect against chronic diseases, including diabetes, cardiovascular disease, cognitive decline, and cancer.

A comprehensive investigation was carried out to find published literature using Web of Science, PubMed, and Scopus. In addition to Boolean operators (AND, OR), keywords such as “superfood,” “bioactive compounds”, “functional foods”, and “health benefits” were integrated. Superfoods, their bioactive ingredients, and potential health benefits based on preclinical or clinical data were the subject of permitted research. Research on isolated or synthesized substances unrelated to superfoods, articles without experimental data, and non-peer-reviewed databases were excluded.

Our research reveals that superfoods include health-promoting phytochemicals, carotenoids, flavonoids, and polyphenols. They may prevent diseases like diabetes, cardiovascular disease, cancer, and obesity. In conclusion, superfoods improve health and wellness in numerous ways.

Superfoods prevent chronic illnesses and improve health. This review discusses the nutritional content and health advantages of superfoods, which may encourage their consumption. More research is needed to promote global health and wellness using superfoods.