Journal of Computational Biophysics and Chemistry

The knowledge base in the field of vaccination research and development has greatly improved. In the present era, utilizing a novel vaccine design and optimization strategy improves the vaccination efficiency and activity. In this regard, a novel drug delivery system produces nanosized, vaccine-loaded carrier molecules, which is called Nanovaccine. The advancement in nanovaccine and improved technology comes under preclinical and clinical trials, whereas different routes of administration strategy are applied against infectious diseases. The nanovaccine has high efficiency and immunogenicity compared to the traditional vaccine. Its long-lasting effect reduces the booster dose as well. One of the factors like routes of administration affects the efficiency of nanovaccine. The parenteral and mucosal vaccination is a traditional administration approach. In order to increase the safety and effectiveness of vaccines, innovative administration methods such as needless injection and polymeric formulations are now being developed. The presented paper shows a mechanism involved in nanovaccine delivery, and a method of administration via a different route, to learn more about their possible effects on immunogenicity, effectiveness, safety, sustained release and dose frequency reduction. The various advanced vaccine delivery methods, with special emphasis on its industrial and regulatory requirements for the higher production of nanovaccine, are also discussed.

Films made with blends of agar and gelatin are usually unstable in aqueous environments and susceptible to temperature, so modifying these films with the addition of compatible compounds is necessary to improve their structural stability, properties, and potential uses. This work determined the effects of adding sorghum procyanidins on the structure, molecular interactions and thermal properties of agar-glycerol-gelatin films. Films were prepared by solution cast method and characterized by Fourier transform infrared spectroscopy (FTIR), X-ray diffraction (XRD), scanning electron microscopy (SEM), thermogravimetric analysis (TGA), differential scanning calorimetry (DSC) and computational methods. Adding sorghum procyanidins to agar-gelatin films plasticized with glycerol produced significant modifications compared to control films. They contributed to the amorphous character and roughness of these films and the film’s microstructure, reducing weight loss and enhancing thermal stability. The predominant interactions among the film components were hydrogen bonds, van der Waals, and $\pi$–$\pi$ interactions.

Background: Pyrazole derivatives have gained attention as potential leads for developing anti-inflammatory and analgesic drugs. Chemical modifications of pyrazole structures offer a strategy to enhance their therapeutic properties, while minimizing undesirable effects.

Objective: This study aimed to synthesize novel pyrazole derivatives through chemical modifications and assess their anti-inflammatory and analgesic activities.

Methods: A series of pyrazole variants were synthesized by reacting various acetophenone derivatives and diethyl oxalate in basic conditions, followed by treatment with glacial acetic acid and hydrazine hydrate. The resulting compounds were further methylated and acetylated. The synthesized compounds were characterized using elemental analysis, ¹H NMR, IR, and MASS spectroscopy. The anti-inflammatory activity was evaluated using the rat paw edema technique induced by carrageenan, while the analgesic activity was assessed using the writhing reflux method.

Results: Among the newly synthesized pyrazole derivatives, compounds 3b, 3e and 3g^′ demonstrated significant anti- inflammatory activity with reduced ulcerogenic potential. Compounds 3d, 3b^′ and 3d^′ exhibited notable analgesic activity compared to the standard drug. The chemical modifications introduced in these derivatives were confirmed through spectroscopic analyses.

Conclusion: The findings of this study highlight the potential of pyrazole derivatives as promising candidates for anti- inflammatory and analgesic drug development. The structural modifications performed in this research improved the therapeutic activities of the compounds, while addressing safety concerns. Further investigations are warranted to elucidate the underlying mechanisms of action and optimize the pharmacological profiles of these novel pyrazole derivatives.

Using first principles, the electrical response of carbon nanocones (NC) to the drug benzamide (BZE) was investigated using density functional theory (DFT). The adsorption energies of BZE at the nanocone’s bottom (Complex I), side (Complex II), and top (Complex III) are −88.35 kcal/mol, −45.46 kcal/mol and −48.73 kcal/mol. The two other adsorptions, Complexes II and III are physisorption, however, the high value of Eads in the case of Complex I with the drop in bond lengths suggests that Complex I adsorption is chemisorption. The electrical conductivity has risen as a result of the considerable decrease in the nanocone energy gap (from 0.63 eV to 0.61 eV, 0.61 eV and 0.60 eV) caused by the adsorption of BZE. It suggests that the nanocones would be a good fit for the electronic sensors and an appropriate choice for BZE detection. Additionally, the BZE adsorption influences the nanocone’s workfunction, which is reduced by approximately 45.19%, 2.8% and 2.05% for complexes I to III. This suggests that the nanocone could be a workfunction-based sensor for the detection of BZE. The increase in binding affinity in complexes reveals that the nanocones will act as a drug delivery carrier. Theoretically, anticipated Raman spectra of BZE and complexes show SERS activity and inactive normal Raman modes are active in the Raman spectrum of complexes. Compounds II and III exhibit weak noncovalent interactions (NCI) and due to the presence of covalent bonding interaction in compound I, significant changes in other bonding and nonbonding electron densities are observed compared to compounds II and III.

Cancer is one of the leading causes of death worldwide and one of the top four causes of premature death in most countries. Several studies have shown that secondary metabolites found in medicinal plants have anticancer, antimutagenic, anti-genotoxic, and chemopreventive effects. Ethnobotany knowledge points to Morinda lucida, Momordica charantia, and Vernonanthura polyanthes as anticancer plants, turning them into promising candidates for cancer treatment. This study analyzed M. lucida, M. charantia, and V. polyanthes compounds to identify potential antioxidant, chemopreventive, and anticancer agents through in silico analysis. We performed pharmacokinetics, biological activities, and toxicological predictions besides molecular docking. Theoretical calculations on thermodynamic grounds of the antioxidant properties were determined using density functional theory. The molecules damnacanthal, momordicin I, and quercetin-3-$O$-rutinoside identified in M. lucida, M. charantia, and V. polyanthes, respectively, presented good anticancer potential and were chosen for the molecular docking study and DFT calculations. According to Lipinski’s criteria, damnacanthal, momordicin I, and quercetin-3-$O$-rutinoside were classified as potential drugs, especially for the pharmacokinetics criteria. Damnacanthal and momordicin I had high absorption in the gastrointestinal treatment, while quercetin-3-$O$-rutinoside had low absorption. These compounds also demonstrated antineoplastic, antimutagenic, and cancer-preventive activity, according to the in silico analysis. In this sense, damnacanthal, momordicin I, and quercetin-3-$O$-rutinoside were chosen to test their potential interactions with the beta estrogen receptor, vascular endothelial growth factor receptor 2, and xanthine dehydrogenase, respectively, and intermolecular interactions were determined. Regarding the antioxidant potential of the structures, two different mechanisms were scrutinized with the help of their respective molecular descriptors, such as hydrogen atom transfer (HAT) and one-electron transfer (ET). In conclusion, this computational study revealed that damnacanthal, momordicin I, and quercetin-3-$O-$rutinoside are promising chemoprotective and anticancer molecules with favorable pharmacokinetics and toxicological properties.

Steroids play essential physiological roles in the living systems, including their role as sex hormones, glucocorticoids, and mineralocorticoids. Usually, they engage in interactions with steroid receptors. Target cell nuclei, cytosol and plasma membranes all have steroid hormone receptors. Cytoplasmic or nuclear, intracellular receptors start the signal transduction process for steroid hormones and cause gene expression alterations over the course of several hours to days. Certain steroid hormones bind to cell surface receptors, including ion channels, G protein-coupled receptors and several nuclear receptors. Dihydropyrimidinones are also significant moieties with important physiological roles. The hybrid molecules can offer several potential biological activities. In this work, we have checked the in silico interaction of some novel cholesterol–dihydropyrimidinones interactions with the sex hormones, mineralocorticoid and glucocorticoid receptors to screen their potential use in the regulation of the sexual cycle or the carbohydrate metabolism or the mineral imbalance.

Phosphoglycerate kinase-1 (PGK1) is an enzyme found in the cells and tissues of the human body. Deficiency of this enzyme leads to deadly neurodegenerative diseases, such as stroke, amyotrophic lateral sclerosis (ALS), Parkinson’s disease and apoptosis. Since there is no ideal drug candidate to cure such diseases by activating this enzyme, this study aimed to discover a new potent candidate from cyanobacteria using in silico pharmacological applications. The preparation of both the protein and the ligands was performed in Maestro 13.2, followed by docking using a range of modules, including Prepwizard, Ligprep, Sitemap, Glidgrid and Glide Dock, with different modes, such as HTVS, SP, XP and Desmond v6.8. Among the 240 docked cyanobacterial metabolites, lyngbyastatin, hoiamide D, lyngbyastatin 4, lyngbyastatin I, lyngbyastatin 7, tigicamide A, hoiamide and symlocamid A, showed remarkable docking and energy values. These compounds exhibit better potency as promising drugs at the target residues than reference molecules, as evidenced by better docking scores, energies, lower root mean square deviation (RMSD) with stronger binding affinities in molecular docking and MD simulations. The study demonstrated that these compounds are the first to be identified as triggers of PGK1, and it was anticipated that these metabolites would show beneficial effects when tested in both in vitro and in vivo studies of such deadly neurodegenerative diseases. The results obtained in the study suggested that these metabolites may provide a beneficial drug effect to reduce the complications associated with PGK1.

Traumatic brain injury (TBI) is caused by the disruption in the brain’s normal function due to some external forces like jolt or blow to the head. While, Parkinson’s disease (PD) is a neurodegenerative disorder which starts with tremor in one hand and gradually worsens over time. The connection between these two important diseases is not yet fully understood. Thus, we have proposed a transcriptome-based approach to identify the interrelation between TBI and PD. Determining the common over-or under gene expression pattern could reveal common pathobiological pathways that may explain the linkage between these two diseases. A total of 609 differentially expressed genes were discovered as commonly expressed genes for both TBI and PD. Further, the pathway studies reveal that nine genes such as NDUFA6, SLC17A7, EMXI, PLPPR1, FEZF2 and DUSP14, SERF1B, HBB and ABR made a significant impact on the disease progression of TBI and PD. In particular, SERF1B and HBB and ABR were considered as the top-ranked genes based on the pathway analysis and functional enrichment calculations. We believe that in-depth study on the identified biomarkers will provide possible treatments strategies to overcome TBI and PD.