Background: The increasing global incidence of breast cancer calls for the identification of new therapeutic targets and the assessment of possible neem-derived inhibitors by means of computational modeling and integrated genomic research. Methods: Originally looking at 59,424 genes throughout 42 samples, we investigated gene expression data from The Cancer Genome Atlas—Breast Cancer (TCGA-BRCA) dataset. We chose 286 genes for thorough investigation following strict screening for consistent expression. R’s limma package was used in differential expression analysis. The leading candidate’s protein modeling was done with Swiss-ADME and Discovery Studio. Molecular docking studies, including 132 neem compounds, were conducted utilizing AutoDock Vina. Results: Among the 286 examined, mitochondrially encoded cytochrome C oxidase III (MT—CO3) turned out to be the most greatly overexpressed gene, showing consistent elevation across all breast cancer samples. Protein modeling revealed a substantial hydrophobic pocket (volume: 627.3 ų) inside the structure of MT—CO3. Docking investigations showed five interesting neem-derived inhibitors: 7-benzoylnimbocinol, nimolicinol, melianodiol, isonimocinolide, and stigmasterol. Strong binding affinities ranging from −9.2 to −11.5 kcal/mol and diverse interactions with MT—CO3, mostly involving the residues Phe214, Arg221, and Trp58, these molecules displayed. With hydrophobic interactions dominant across all chemicals, fragment contribution analysis revealed that scaffold percentage greatly influences binding effectiveness. Stigmasterol revealed greater drug-likeness (QED = 0.79) despite minimal interaction variety, while 7-benzoylnimbocinol presented the best-balanced physicochemical profile. Conclusion: Connecting traditional medicine with current genomics and computational biology, this work proposes a methodology for structure-guided drug design and development using neem-derived chemicals and finds MT—CO3 as a potential therapeutic target for breast cancer.

The research paper investigates the phytochemicals of watermelon (Citrullus lanatus) as potential novel inhibitors of phosphodiesterase type 5 (PDE5), which is essential for treating erectile dysfunction and pulmonary arterial hypertension. A total of 150 compounds were screened against five PDE5 enzyme structures using molecular docking techniques with Chimera and AutoDock Vina. Interactions were visualized with Chimera and PyMOL, while SwissADME was employed to predict pharmacokinetic properties, and ProTox-II was utilized to assess toxicity. Lunamarine has emerged as a promising candidate for PDE5 inhibition, demonstrating superior pharmacokinetics and favorable toxicity profiles. It exhibited high gastrointestinal absorption and permeability across the blood–brain barrier, potentially outperforming existing inhibitors. The binding energies ranged from − 9.421 to − 9.55 kcal/mol across various PDE5 targets, indicating comparable efficacy. Structural analyses revealed significant hydrophobic interactions with PHE820 and LEU725, as well as hydrogen bonding with TYR612, which are crucial for the formation of the binding pocket. Lunamarine’s effect on catalytic zinc coordination was evidenced by receptor-ligand distances of 3.6 to 3.7 Å. These findings suggest that lunamarine may provide advantages over current therapies, particularly regarding its penetration of the central nervous system. The study recommends further in vitro and in vivo validation of lunamarine's efficacy and safety, as well as an exploration of its potential in other conditions related to PDE5. This research could pave the way for the development of watermelon-derived nutraceuticals for disorders associated with PDE5.

Background: Dental caries arise from polymicrobial biofilms and require interventions that address both local virulence and systemic burden. Methods: A curated set of 124 neem-derived phytochemicals was screened against Streptococcus mutans glucansucrase (3AIC) and Staphylococcus aureus DNA gyrase B (3U2D) using harmonized AutoDock Vina parameters. Ligand standardization and receptor preparation followed conventional protocols. Results: The most favorable docking scores reached −10.7 kcal·mol⁻¹ for 3AIC and −8.9 kcal·mol⁻¹ for 3U2D. Redocking produced pose RMSD values of 1.52 Å (3AIC) and 0.96 Å (3U2D). Per-receptor ADMET profiles for the six top-ranked compounds indicated median logP values of 4.93 (3AIC) and 4.52 (3U2D), median TPSA values of 80.3 and 62.9 Ų, median rotatable bonds of 2.5 and 1.0, and median QED values of 0.41 and 0.76, respectively. Conclusions: An integrated, dual-target screen prioritized neem constituents with plausible local anti-cariogenic activity and physicochemical features compatible with systemic disposition. These in silico findings motivate targeted experimental validation.

Orexinergic system dysfunction is the fundamental basis for several neurological illnesses like narcolepsy, insomnia, and drug dependency, yet none of the existing medications are subtype receptor specific. This study examines 124 chemicals from neem to determine if they can be utilised as specific orexinergic receptor modulators using advanced computational methods. The methodology includes detailed clustering, pharmacophoric interaction, pharmacokinetic, statistical, and clustering analyses. Molecular property profiling indicated the majority of the compounds exhibit excellent drug-like qualities (MW 350–450 Da, LogP 0–2), while principal component analysis captured 100 % structural variability between two components (92.5 % and 7.5 %, respectively). Molecular docking simulations indicated selective binding to the 6V9S receptor (-11.3 to −4 kcal/mol) over 4S0V (-9.7 to −4 kcal/mol). Lead compounds Neem_PDB_10257 (Tirucallol) (-11.3 kcal/mol) and Neem_PDB_12072821 ([(5 R,7 R,8 R,9 R,10 R,13S,17 R) −17-(2-methoxy-5-oxo-4,4,8,10,13-pentamethyl-3-oxo-5,6,7,9,11,12,16,17-octahydrocyclopenta[a]phenanthren-7-yl] acetate) were particularly 6V9S selective (>2 kcal/mol difference), whereas Neem_PDB_10160319 ((4S,4aS,5S,10S,13S,14S,17–4,4,10,13,14-pentam −1, 2, 3, 5, 6, 7, 11, 12, 15, 17-decahydrocyclopenta[a]phenanthren-16-one) was most sensitive towards 4S0V. Two top-ranked compound families were discovered by hierarchical cluster analysis with a distance requirement of 35 units, and receptor-specific dendrograms revealed distinctive subcluster branching patterns (4S0V: 5.5 and 6.7 unit subclusters; 6V9S: 7.1 and 7.2 unit subclusters). Interaction pattern (heatmap analysis) identified major interaction hotspots, including TYR348, TRP120, PHE227, and HIS350. Neem_PDB_163184214 (Meliatetraolenone) specifically targeted ASN318 in 6V9S, while Neem_PDB_54580354 (7-Benzoylnimbocinol) favored interaction with GLN134 in 4S0V (>90 interactions). These findings dispute the "one-pharmacophore" theory for orexinergic modulators, showing that intentional functionalization of NEM templates can deliver subtype-selective treatments with maximal sleep-wake modulation and low off-target effects.