A paradigmatic approach to the molecular descriptor computation for some antiviral drugs.

In theoretical chemistry, topological indices are commonly employed to model the physico-chemical properties of chemical compounds. Mathematicians frequently use Zagreb indices to calculate a chemical compound's strain energy, melting point, boiling temperature, distortion, and stability. The current global pandemic caused by the new SARS-CoV-2, also known as COVID-19, is a significant public health concern. Various therapy modalities are advised. The issue has become worse since there hasn't been enough counseling. Researchers are looking at compounds that might be used as SARS and MERS therapies based on earlier studies. In several quantitative structure-property-activity relationships (QSPR and QSAR) studies, a variety of physiochemical properties are successfully represented by topological indices, a sort of molecular descriptor that just specifies numerical values connected to a substance's molecular structure. This study investigates several irregularity-based topological indices for various antiviral medicines, depending on the degree of irregularity. In order to evaluate the effectiveness of the generated topological indices, a QSPR was also carried out using the indicated pharmaceuticals, the various topological indices, and the various physiochemical features of these antiviral medicines. The acquired results show a substantial association between the topological indices being studied by the curve-fitting approach and the physiochemical properties of possible antiviral medicines.

A preliminary survey for Wolbachia and bacteriophage WO infections in Indian mosquitoes (Diptera: Culicidae).

Maternally inherited Wolbachia endosymbiotic bacteria are known to induce various kinds of reproductive alterations in their arthropod hosts. It has been proposed that this bacterium can be used as a tool for gene drive system in mosquitoes and also for the reduction of population size and modulating population age structure in order to reduce disease transmission. In the present study, we carried out a survey to determine the prevalence of Wolbachia and its phage WO infection in Indian mosquitoes and classified Wolbachia infection into groups A and B based on extensive polymerase chain reaction assay using Wolbachia specific wsp and orf7 gene primers. Out of 20 fieldcaught mosquito species, eight species have shown to be infected. Singly infected with Wolbachia A was found in two species and B group found in four species, while double infection with AB group were found in two species. All the screened mosquito species with positive Wolbachia infection were also infected with phage WO. The knowledge of variation in Wolbachia and phage WO infection rates and inferred susceptibility to infection among different mosquito genera has fundamental implications for designing and successful application of Wolbachia based vector-borne disease control strategies.

Regioisomeric SCFA attachment to hexosamines separates metabolic flux from cytotoxicity and MUC1 suppression.

Chemical biology studies, exemplified by metabolic glycoengineering experiments that employ short chain fatty acid (SCFA)-hexosamine monosaccharide hybrid molecules, often suffer from off-target effects. Here we demonstrate that systematic structure-activity relationship (SAR) studies can deconvolute multiple biological activities of SCFA-hexosamine analogues by demonstrating that triacylated monosaccharides, including both n-butyrate- and acetate-modified ManNAc analogues, had dramatically different activities depending on whether the free hydroxyl group was at the C1 or C6 position. The C1-OH (hemiacetal) analogues enhanced growth inhibition in MDA-MB-231 human breast cancer cells and suppressed expression of MUC1, which are attractive properties for an anticancer agent. By contrast, C6-OH analogues supported high metabolic flux into the sialic acid pathway with negligible growth inhibition or toxicity, which are desirable properties for glycan labeling in healthy cells. Importantly, these SAR were general, applying to other hexosamines ( e.g., GlcNAc) and non-natural sugar "scaffolds" ( e.g., ManNLev). From a practical standpoint, the ability to separate toxicity from flux will facilitate the use of MOE analogues for cancer treatment and glycomics applications, respectively. Mechanistically, these findings overturn the premise that the bioactivities of SCFA-monosaccharide hybrid molecules result from their hydrolysis products ( e.g., n-butyrate, which acts as a histone deacetylase inhibitor, and ManNAc, which activates sialic acid biosynthesis); instead the SAR establish that inherent properties of partially acylated hexosamines supersede the cellular responses supported by either the acyl or monosaccharide moieties.

Gangliogenesis in the enteric nervous system: roles of the polysialylation of the neural cell adhesion molecule and its regulation by bone morphogenetic protein-4.

The neural crest-derived cells that colonize the fetal bowel become patterned into two ganglionated plexuses. The hypothesis that bone morphogenetic proteins (BMPs) promote ganglionation by regulating neural cell adhesion molecule (NCAM) polysialylation was tested. Transcripts encoding the sialyltransferases, ST8Sia IV (PST) and ST8Sia II (STX), which polysialylate NCAM, were detectable in fetal rat gut by E12 but were downregulated postnatally. PSA-NCAM-immunoreactive neuron numbers, but not those of NCAM, were developmentally regulated similarly. Circular smooth muscle was transiently (E16-20) PSA-NCAM-immunoreactive when it is traversed by migrating precursors of submucosal neurons. Neurons developing in vitro from crest-derived cells immunoselected at E12 with antibodies to p75(NTR) expressed NCAM and PSA-NCAM. BMP-4 promoted neuronal NCAM polysialylation and clustering. N-butanoylmannosamine, which blocks NCAM polysialylation, but not N-propanoylmannosamine, which does not, interfered with BMP-4-induced neuronal clustering. Observations suggest that BMP signaling enhances NCAM polysialylation, which allows precursors to migrate and form ganglionic aggregates during the remodeling of the developing ENS.

The biosynthesis of isopimpinellin.

Bergapten and xanthotoxin, labelling in the methyl group wich carbon-14 or tritiated at three skeletal carbons, were administered to leaves of Heracleum lanatum and to cell cultures of Ruta graveolens. In all experiments xanthotoxin was the more efficient precursor of isopimpinellin, although bergapten was always incorporated to a measurable extent. Double-labelling experiments showed that both precursors, especially bergapten, underwent considerable demethylation (and presumably remethylation) before conversion to isopimpinellin. 5-Hydroxyxanthotoxin and 8-hydroxybergapten were both O-methylated by cell-free extracts of Ruta cells to isopimpinellin, in reactions mediated by discrete O-methyltransferases. 8-Hydroxy[Me-14C]bergapten was converted with a high degree of incorporation to isopimpinellin by Ruta cells in vivo, and it is suggested that the preference for the pathway via xanthotoxin may be due to more rapid hydroxylation of this substrate.