Kerala State Council for Science, Technology and Environment

Introduction: The continued exploration of natural resources holds great potential for identifying novel and effective anticancer compounds. In this study, we aim to analyze the anticancer potential of the methanol extract from the rhizome of the ethnomedicinal plant Corallocarpus epigaeus against skin cancer. Methods: A methanol extract of the rhizome (CME) was prepared by successive solvent extraction of the dried powder using a polarity gradient. Anticancer potential of CME was assessed by MTT (3- (4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide) - cell viability assay. Antiproliferative activity of CME against skin cancer cells was confirmed by fluorescent microscopy and in vitro scratch assay. The cell death mechanism exhibited by CME was analysed by FACS (Fluorescence- Activated Cell Sorting) and Western blot analysis. Results: The MTT assay revealed a significant cytotoxic effect of CME against skin cancer cells, especially the melanoma skin cancer cell line (IC50 0.15 μg/mL), and its non-toxicity towards normal fibroblast cells. In vitro scratch assay and acridine orange/ethidium bromide staining confirmed the cytotoxic effect against the melanoma cell line, A375. FACS analysis of CME-treated A375 cells stained with FITC-Annexin V/PI revealed that the cytotoxic effect was mediated through apoptotic cell death. Additionally, immunoblot analysis revealed the activation of p53 and upregulation of the Bax protein, indicating the involvement of the p53-mediated apoptotic pathway. Discussion: The present study highlights the potent anticancer efficacy of a bioactive extract (CME) from Corallocarpus epigaeus against both melanoma and NMSC skin cancer cells, with preliminary evidence of apoptosis induction in melanoma. Ongoing work in our lab aims to isolate the active compound(s), characterize the phytochemicals, elucidate the molecular mechanisms underlying the anticancer activity, and explore the potential of CME as a topical chemotherapeutic agent for treating melanoma. Conclusion: Our study provides evidence for the potential of CME against skin cancer cells, particularly melanoma, and warrants further exploration of its chemotherapeutic efficacy against melanoma.

Conventional pharmacological interventions for erectile dysfunction (ED) primarily rely on the phosphodiesterase-5 (PDE5) inhibitors such as sildenafil, tadalafil, vardenafil, and avanafil that have side effects despite their therapeutic effects. PDE5 is the primary cyclic guanosine monophosphate-degrading enzyme located in the smooth muscles of the corpus cavernosum in the penile tissue that helps in relieving erection. Natural products and phytochemicals are viable sources of molecular leads for drug discovery and development and, thus, offer prospects for innovation in ED treatment. This in silico study reports the screening of phytochemicals from the plant Tribulus terrestris with an eye to identify molecular candidates that inhibit PDE5. Natural products-based compounds that selectively target PDE5 are poised to be useful in clinical management of ED, and potentially with lesser side effects. The following top three phytochemicals identified from T. terrestris showed higher negative binding affinities for the PDE5 enzyme: diosgenin,dehydro (-11.1 kcal/mol), ruscogenin (-11.1 kcal/mol), and hecogenin (-10.3 kcal/mol) compared with the control drug sildenafil (-8.8 kcal/mol). Hydrogen bonds and Van der Waals interactions were the predominant forces influencing the interactions formed in the protein-ligand complexes. The ΔGbind binding free energies for these top three phytochemicals, diosgenin,dehydro, ruscogenin, and hecogenin, were -19.99 ± 5.99 kcal/mol, -9.05 ± 5.16 kcal/mol, and -14.11 ± 5.33 kcal/mol, respectively. Importantly, diosgenin,dehydro, a saponin obtained from T. terrestris, was identified as a particularly promising candidate for PDE5 inhibition by virtue of its higher negative binding affinity and, therefore, displaying a potential in drug discovery and development for ED. In addition, in silico pharmacokinetic analysis and toxicity assessments support the prospects of these T. terrestris-derived phytochemicals for future in vitro and invivo research for innovation in ED therapeutics.

This study uses density functional theory (DFT) calculations at the M06-2X/6-311 + G(d,p) level to explore the potential of main group non-metals (X = O, N, S, P) to form hypervalent ylides (RmX+-YRn -2 -). Substituent effects (R = alkoxy, alkyl, phenyl, H, NH2, NMe2, halogens) on the stability of these ylides and their neutral counterparts (Rm- 1X-YRn -1) are analyzed across various X → Y bonding scenarios. Fluorine-substituted ylides (e.g., NhO/F, ShO/F, ShS/F, PhO/F) and PhO/OMe exhibited the highest stability compared to their neutral forms. Bond length and Wiberg bond order analyses reveal significant double bond character of the X-Y bond, confirming the hypervalent structure of the molecule. Molecular electrostatic potential (MESP) analysis shows reduced charge separation and delocalized electron density of the molecule, supporting a hypervalent ylene resonance form (RmX = YRn -2). These findings provide insights into the stability and electronic structure of hypervalent molecules, aiding the design of novel compounds.

Hydroxy-substituted aromatic N-heterocycles, including hydroxy pyridine (py), dihydroxy naphthyridines (nt), and trihydroxy pyridonaphthyridines (pn), have been investigated for their potential as CO2 adsorbents using density functional theory (DFT) calculations. Building on the pioneering work of Luo et al., who demonstrated exceptional CO2 capture capacities in pyridine-containing anion-functionalized ionic liquids, this study extends the exploration to a broader range of N-heterocycles. These N-heterocycles exhibit exceptional CO2 capture capabilities, driven by cooperative interactions between nitrogen and oxygen centres with CO2. The adsorption capacity increases with the number of nitrogen centres and hydroxy groups, with py, nt, and pn systems binding one, two, and three CO2 molecules, respectively. Notably, anionic N-heterocycles exhibit dramatically improved CO2 adsorption compared to their neutral counterparts, forming covalent bonds with CO2. The presence of counter cations, such as lithium or tetramethylphosphonium ions, further stabilizes CO2 adsorption, resulting in shorter interaction distances and higher exergonic free energy values. Solvent effects modeled using monoethanolamine (MEA) indicate a modest reduction in interaction energies for neutral and anionic systems, while ion-paired systems exhibit enhanced CO2 affinity in solution. Additionally, molecular electrostatic potential (MESP) analysis highlights the key adsorption sites and charge delocalization mechanisms that facilitate CO2 capture. The study also finds that enol-keto transformations, which could lead to CO2 conversion into carboxylates, are energetically unfavorable due to the loss of aromatic stability. These findings underscore the potential of hydroxy-substituted N-heterocycles, particularly in their anionic and cation-stabilized forms, as promising candidates for efficient CO2 capture. The insights gained from this study provide valuable guidelines for the design of next-generation CO2 sequestration materials and highlight new directions for experimental validation and real-world applications.

ABSTRACT An assessment was conducted on the performance of Rothamsted Carbon Model (RothC) model’s in simulating Soil Organic Carbon (SOC) dynamics over a 112-year period involving organic and mineral fertilization practices in a sandy-loam Alfisol. The crop rotation of the experiment included maize and sunflower. The model performance was evaluated by Coefficients of Root Mean Square Error (RMSE) and Efficiency factor (EF). Subsequently, model was utilized to forecast SOC dynamics over a 25-year period under similar pedoclimatic conditions. The results of the RothC simulations demonstrated Nitrogen, Phosphorus and Pottassium (NPK) + Farm Yard Manure (FYM) increased SOC stocks at the 0–15 cm soil depth (RMSE = 1.36, EF = 0.66). The SOC stocks reached steady state for the treatments FYM (every year) (RMSE = 0.99; EF = 0.49). RothC clearly simulated SOC reductions in control plot (RMSE = 12.37; EF = 0.58) and inorganic fertilizers applied plot (RMSE = 1.17; EF = 0.64). The carbon sequestration potential of the treatment which received NPK+ FYM is 147 kg ha−1 yr−1 during 2032 and it showed an improvement over the future years. Similarly, FYM treatment plot showed a sequestration potential of 96 kg ha−1 yr−1 and it showed a static rate in the future trend. However, 100% NPK plot shows declining trend which was 59 kg ha−1 yr−1. In conclusion, our findings indicate that the RothC model effectively predicts C dynamics in the Permanent Manurial Experiment plot, provided accurate initialization and appropriate parameterization of the model are ensured.