Balakumar Chandrasekaran

In this study, nine derivatives of 3,10-dihydro-2 H -1,3-oxazepino[7,6- b ]indole (1–9), which combine two bioactive pharmacophoric cores, were synthesized and tested for antibacterial activity against five pathogenic bacterial strains. The resazurin-based microdilution plate method was used to determine minimum inhibitory concentration (MIC) values. Derivative 6 displayed the greatest potency (MIC = 0.0048 mg/mL against S. typhimurium ). Molecular docking suggested possible interactions between the ligands and peptidoglycan glycosyltransferases. In silico analysis using SwissADME, ProTox 3.0, Cytotoxicity Predictor Online, quantitative structure–activity relationship (QSAR), and quantitative structure–activity/toxicity (QSAT) modeling suggested high gastrointestinal absorption, adherence to drug-likeness rules, and low predicted cytotoxicity across 198 human cell lines. Toxicological predictions suggested nontoxic behavior of all derivatives, with lower predicted activity in normal fibroblasts than in tumor-derived lines. The findings identify derivative 6 as the most active antibacterial candidate and derivative 5 as a safe lead with balanced antimicrobial potential, supporting further antibacterial drug research and the development of these scaffolds for clinical application.

The human genome encodes a wide variety of protein kinases that regulate multiple cellular functions.

Background/Objectives: Psychobiotics are live microorganisms that, when administered in appropriate amounts, can enhance mental health. Through the production of neuroactive metabolites, regulation of immune responses, and interactions along the gut–brain axis, they modulate host neurophysiology. However, significant strain-specific variability exists in their metabolic capabilities, colonization potential, and functional interactions, necessitating a systematic approach for psychobiotic strain selection. Methods: In the present study, an integrated in silico systems biology approach combining comparative genomics, genome-scale metabolic modeling, network pharmacology, molecular docking, molecular dynamics, and ADMET analysis was employed to computationally evaluate the therapeutic potential and molecular interactions of a quercetin-psychobiotic co-delivery system for managing depression by modulating the gut–brain axis. Results: Comparative genomic analysis of candidate psychobiotic strains from the genera Bifidobacterium and Lactobacillus predicted the presence of key functional genes involved in neuroactive metabolite production, immune modulation, oxidative stress tolerance, and adhesion. The presence of acetate-producing pathways alongside the absence of classical butyrate biosynthesis genes indicated an indirect contribution to short-chain fatty acid production via microbial cross-feeding interactions. Genome-scale metabolic Modeling under the conditions of quercetin supplementation predicted a significant inter-strain variation in terms of predicted biomass flux, nutrient utilization, and metabolic adaptability. Results of molecular docking showed that the binding energies were in the range of −5.854 to −9.489 kcal/mol. Conclusions: Collectively, these in silico findings provided a computational basis for the selection of psychobiotic strains and predicted that a combination of psychobiotics and quercetin could present a promising strategy for the modulation of the gut–brain axis.

Glycemic variability is a stand-alone risk factor for diabetic complications. Background/Objectives: We investigated whether combining quercetin-rich Allium cepa L. (white onion) juice with the sodium-glucose cotransporter-2 (SGLT2) inhibitor dapagliflozin could reduce glycemic variability beyond that achieved with monotherapy in experimental diabetes. Methods: Wistar rats were made diabetic with streptozotocin (35 mg/kg) and maintained for 60 days in the following groups: vehicle, dapagliflozin (0.1 mg/day), fresh onion juice (5 mL twice daily), and dapagliflozin + fresh onion juice (5 mL twice daily). Diabetic Wistar rats (n = 10/group) were gavaged with vehicle, dapagliflozin (0.1 mg/day), fresh onion juice (5 mL twice daily), or both. The juice was expected to contain phytochemicals (quercetin derivatives and organosulfur compounds) based on published reports on similar A. cepa cultivars. A validated immunoassay was used to measure glycated hemoglobin (HbA1c) every 10 days. All treatments reduced HbA1c to the same level (~7.1–7.2%) as compared to diabetic controls (9.0 ± 0.3%) (p < 0.001), though only the combination treatment reduced glycemic variability (HbA1C coefficient of variation 3.9 ± 0.6% vs. 7.8 ± 1.2% with dapagliflozin and 11.2 ± 1.8% with onion) (p < 0.001). Results: Across the 10-day sampling schedule, the combination kept HbA1c within a narrow 6.8–7.2% band, whereas the monotherapies fluctuated more widely; because intraday and postprandial glucose were not captured, effects on short-term excursions could not be directly assessed. There were no cases of severe hypoglycemia and only infrequent and non-repeated cases of mild hypoglycemia. Conclusions: In this exploratory, hypothesis-generating study, the additive interaction between onion phytochemicals and dapagliflozin was associated with lower glycemic variability via mechanisms proposed in the literature; quercetin-rich A. cepa juice may therefore warrant further investigation as an adjunct in diabetes management, pending batch-specific phytochemical characterization and confirmatory studies.

Background/Objectives: Until now, there have been no suitable medicines to treat infections caused by the Ebola virus. Cistus incanus, a traditional medicinal plant, contains several phytocompounds exhibiting antioxidant and anti-inflammatory properties. Methods: In this research, the molecular level interactions of the phytocompounds of Cistus incanus were investigated for their antiviral potential against the active site of VP40 protein of Ebola virus using in silico molecular docking. Further, the potential compounds were assessed for their stability in the protein using molecular dynamics (MD) simulations. Results: Methyl gallate, catechin, and quercetin showed excellent docking scores of −9.8, −8.8, and −7.7 kcal/mol, respectively, and favorable interactions with the target protein. These complexes showed good stability over the 100 ns MD simulation time. In addition, the phytocompounds displayed favorable pharmacokinetics and drug-like properties. Conclusions: Our study offers the antiviral potential of phytocompounds (methyl gallate, catechin, and quercetin) of Cistus incanus, suggesting their suitability as lead candidates for the treatment of Ebola viral infection.

The annual burden of gastric cancer (GC) is increasing, highlighting a major threat to global public health. An important contributing factor to the increased fatality of the disease is the late stage at which GC is usually detected. Recent advancements in genomic and molecular studies have spearheaded the discovery of novel biomarkers for early-stage GC. Enabled by metabolomic, genetic, epigenetic, and proteomic signatures, these biomarkers have the potential to change the diagnostic outlook for GC. Such biomarkers would allow the detection of disease in its early stages, thereby improving the quality of life of those affected by this disease and also lowering the mortality rate. This review aims to provide a thorough overview of the novel biomarkers in GCs. Furthermore, this review addresses the mechanism by which these biomarkers are linked to the detection of GC and their possible utilization in clinical settings. This review comprises several novel biomarkers such as heat shock protein family A6 (HSPA6), annexin A11 (ANXA11), cell division cycle 42 (CDC42), fibroblast activation protein-alpha (FAP), hepcidin antimicrobial peptide (HAMP), solute carrier family 25 member 4 (SLC25A4), serpin peptidase inhibitor clade H member 1 (SERPINH1), cystatin B, deleted in malignant brain tumors 1 (DMBT1), nuclear paraspeckle assembly transcript 1 (NEAT1), N6-methyladenosine-related lncRNAs, circular RNAs, and proteinase 3 (PRTN3). Thus, the aim of this review is to gather and incorporate the current state of knowledge on this topic to point out the need for persistent research and innovation in the field of identification of GC biomarkers. This will enable the opportunity for new and more effective strategies for combating GC, which will further reduce its global burden and improve patient survival.

Background: Various routes of drug administration are available for psoriasis treatment. However, there is an urgent need for novel and improved therapeutic options. Hence, our study aimed to develop a nanostructured lipid carrier (NLC) gel of hesperidin (HPD) using a systemic QbD approach for an effective treatment of psoriasis. Methods: Initially, HPD-NLC was optimized with independent variables (drug content, amount of liquid lipid, total lipid, and surfactant concentration) using Box–Behnken Design to assess dependent variables (particle size, size distribution, and entrapment efficiency). HPD-NLC was developed using the high-shear homogenization technique. The characteristics of nanoformulation such as particle size, morphology [transmission electron microscopy (TEM) and differential scanning calorimetry (DSC)], crystallinity [powder X-ray diffraction (XRD)], and chemical interactions [Fourier transform infrared spectroscopy (FTIR)], the drug entrapment efficiency (%EE), and the drug release were investigated. Franz-diffusion cell was utilized to perform in vitro diffusion study, and an imiquimod-induced psoriasis model was used for in vivo study. Results: The optimized HPD-NLC exhibited a spherical shape with particle size of 125.7 nm, polydispersity index (PDI) of 0.36, and entrapment efficiency of 52.26% w/w. Further, different techniques validated the reduced crystallinity of the hesperidin. The in vitro diffusion study highlighted the sustained and anomalous diffusion of the drug from NLC gel. In the in vivo study, the HPD-NLC-Gel-treated group displayed normal skin with minimal keratosis, while the drug-loaded gel group exhibited signs of hyperkeratosis and parakeratosis signs. Conclusions: HPD-NLC gel showed promising advancement in nanotechnology-based psoriasis treatment and the results of this study open the door for the application of topical HPD-NLC-Gel clinically.