NOPR Collection:

Computational, Spectroscopic, Hirshfeld surface, Molecular docking and Topological studies on 2-bromo-5-methylpyridine as potent anti-cancer agent

Tue, 01 Jul 2025 00:00:00 GMT

Title: Computational, Spectroscopic, Hirshfeld surface, Molecular docking and Topological studies on 2-bromo-5-methylpyridine as potent anti-cancer agent Authors: Senthil Kumar, J; Siva Jyothi, N; Sumathi, S; Karthik, N; Jeyavijayan, S Abstract: 2-Bromo-5-methylpyridine (2BMP) has been found to show FTIR and FT-Raman spectra in the 3500-400 cm-1. The density functional theory (DFT/B3LYP) method was applied to determine the structure, frequencies, Raman activities, and infrared intensities of the molecule using 6-311++G(d,p). The study of molecular orbital contributions has been done with the use of the DOS spectrum. Natural bond orbital (NBO) analysis has been used to calculate the stability of a molecule resulting from hyper-conjugative π→π* exchanges and charge delocalisation. Furthermore, the 2BMP's Fukui function, Mulliken charges, and NMR chemical shifts have been examined. Thermodynamic, LOL, and ELF characteristics were investigated topologically in relation to temperature. The binding affinities of breast cancer inhibitors like 1ERE, 1AQU, and 4OAR are found as -5.1, -5.4, and -5.4 Kcal/mol from the docking study. Prescription medications and these affinities are similar. Through ADMET analysis, the degree of drug-likeness in a molecule has been investigated and evaluated. Page(s): 683-699

Tracing the evolutionary history of novel hormone asprosin: An in silico study across vertebrates

Tue, 01 Jul 2025 00:00:00 GMT

Title: Tracing the evolutionary history of novel hormone asprosin: An in silico study across vertebrates Authors: Sathoria, Priyanka; Chuphal, Bhawna; Rajagopalan, Vaishnavi; Kajal; Singh, Arya; Tyagi, Khushi; Singh, Jyoti; Rai, Umesh; Roy, Brototi Abstract: Although, asprosin is implicated in regulation of various physiological functions and metabolic disorders, there are no reports in non-mammalian vertebrates except in fish Channa punctata. Hence, in this study we explore the asprosin across the vertebrate group through in silico analysis. This novel hormone is by product of enzymatic cleavage of profibrillin protein (encoded by FBN1 gene) by furin protease. We have focused on the comparative analysis of physicochemical properties, structure and evolutionary relationship of putative asprosin. The physicochemical properties of putative asprosin across the vertebrate groups revealed thermostability, ex vivo stability and its hydrophilic nature. The secondary and tertiary structures of putative asprosin revealed beta strands that provide the stability and help in folding of protein. The sequence homology of putative asprosin primary sequence reveals more than 50% conservation across the vertebrates. The crucial post-translational modifications such as phosphorylation and glycosylation are present in putative asprosin. Asprosin was observed to be subjected to purifying selection, suggesting limited changes in structure and function of asprosin over extensive evolutionary period. Further, phylogenetic analysis of asprosin showed that bony fishes form a separate clade distinct from mammals, birds, reptiles and amphibians. This study for the first time provides an insight into the conservation of fbn1 encoded profibrillin protein, furin cleavage site in profibrillin protein and its C-terminal cleavage product, asprosin, across the vertebrate groups. The conserved physicochemical properties and strong purifying selection showed that asprosin was under strong evolutionary pressure. Page(s): 700-711

Understanding the conformational dynamics of an intrinsically disordered protein bound to a small molecule

Tue, 01 Jul 2025 00:00:00 GMT

Title: Understanding the conformational dynamics of an intrinsically disordered protein bound to a small molecule Authors: Sharma, Babli; Satish Kumar Mattaparthi, Venkata Abstract: Intrinsically disordered proteins (IDPs) have been implicated in a wide range of human diseases. Due to their intrinsic conformational variability, IDPs are generally not effective for conventional structure-based drug design. Recently, ZZW- 115 has been identified as a promising inhibitor of NUPR1 (an IDP whose overexpression is involved in various cancers), offering a potential lead for the development of novel cancer therapies. Understanding the conformational dynamics is crucial for comprehending the inhibitory action of ZZW-115, revealing the binding modes and dynamic interactions between ZZW-115 and NUPR1. Here, we present a computational study employing atomic-level Molecular dynamics (MD) simulations coupled with Umbrella sampling (US) to investigate the binding of ZZW-115 to NUPR1, elucidating the conformational changes and dynamics involved in the interaction. The Potential of Mean Force (PMF) plot showed a minimum value of 9Å at NUPR1-ZZW-115 separation with a dissociation energy of 2 kcal/mol. From Root Mean Square Deviation (RMSD) and secondary structure analysis, the conformational dynamics of NUPR1 was found to be varied as a function of its centre of mass (CoM) distance from ZZW-115. The NUPR1-ZZW-115 complex with the lowest potential energy extracted from the PMF plot was used to study the conformational dynamics of NUPR1 in unbound and complex form. The study reveals specific residues and binding pockets in NUPR1's disordered region that bind to ZZW-115, providing valuable insights into its inhibitory mechanism, enabling the development of effective drug design for therapeutic purposes. Page(s): 712-723

Unveiling the mitigating effect of matcha-silver nanoparticles on radiationinduced ovarian injury in rats

Tue, 01 Jul 2025 00:00:00 GMT

Title: Unveiling the mitigating effect of matcha-silver nanoparticles on radiationinduced ovarian injury in rats Authors: Khateeb, Sahar; Faridi, Uzma; Obidan, Amnah; Albalawi, Mody; A Alwabsi, Hayam; M Almutairi, Fahad; I Alalawy, Adel; S Mohamed, Mervat Abstract: Radiotherapy, an essential cancer treatment, poses significant risks to ovarian tissue, especially during whole-body irradiation treatments. This study aims to evaluate the efficacy of silver nanoparticles derived from matcha green tea (M-AgNPs) inmitigating oxidative stress and apoptosis caused by gamma radiation in rat ovaries. The thirty-six rats were partitioned into six groups. Group 1: control; Group 2: 3; normal rats received matcha and M-AgNPs (10 mL/kg) orally for 14 days respectively; Group 4: rats subjected to 6 Gy whole-body gamma radiation. Groups 5 and 6 of irradiated rats received daily oral administrations of matcha and M-AgNPs (10 mL/kg) for a duration of 14 days, respectively. Biochemical and histological investigations were conducted to evaluate oxidative stress, apoptosis, and ovarian tissue architecture. Radiation significantly (P< 0.05) decreased total antioxidant capacity (TAC) and elevated 8-OHdG levels, indicating oxidative damage. The treatment with M-AgNPs mitigated these effects by reducing the concentration of 8-OHdG and enhancing TAC, thereby restoring antioxidant balance. Furthermore, radiation markedly (P< 0.05) elevated p53 and ERK1 expression levels, whereas M-AgNPs treatment significantly (P< 0.05) diminished p53 and ERK1 expression levels in ovarian tissue. Radiation causes several forms of DNA damage, while the treatment with M-AgNPs mitigated this damage. Histopathological evaluations exhibited considerable improvements in the histological characteristics of ovarian tissue following the administration of M-AgNPs in comparison to irradiated rats. According to these findings, M-AgNPs represent one of the most promising methods for mitigating radiation-induced ovarian damage. Additional work is necessary to clarify particular molecular pathways and their long-term effects Page(s): 724-732