Biology subjects

P, R.

Publications and source records attributed to P, R..

3 recordsLinked to original sources

bioRxiv2025

IN SILICO DRUG DISCOVERY FOR NDM -1 METALLO β LACTAMASE INHIBITORS for KLEBSIELLA PUEUMONIAE

In every region of the world, antibiotic resistance is increasing to dangerously high levels. Our ability to cure widespread infectious diseases is being threatened by the emergence of new resistance mechanisms. Klebsiella pneumoniae is one of the most prevalent nosocomial Gram-negative bacteria in the world. NDM-1 is a brand-new class of metallo-{beta}-lactamase (MBL) that makes the bacteria almost total resistant to all {beta}-lactam antibiotics, including penicillins, cephalosporins and carbapenems. Dangerous infections could develop if NDM-1 switches to a bacterium that is already resistant to antibiotics. It could be untreatable and spread quickly among humans. Using the available insilico tools, in the present research work, an attempt has been made to develop inhibitors for NDM-1 {beta} Lactamase of K. pneumoniae. In the present study, 8 standard ligands were identified and docked against the NDM-1 protein using PyRx. Among these standards, Sulfonamide was selected as the best compound and virtual screening of a large number of sulfonamide moieties was conducted with the identified active site in NDM-1 protein using PyRx. On analyzing the obtained results, about 60 molecules were selected as best hits for Docking studies and ADMET studies. On analyzing the ADMET properties and binding energies of the top hits, (3Z)-N-hydroxypenta-1,3-diene-2-sulfonamide (Pubchem CID 118156306) and N-hydroxyfuran-2-sulfonamide (Pubchem CID 46175386). Molecular dynamics simulations were carried out on the complxes formed by these 2 compounds with target protein and the results showed the complexes were stable which validated the earlier findings. Based on the findings of the study, it was concluded that (3Z)-N-hydroxypenta-1,3-diene-2-sulfonamide (Pubchem CID 118156306) and N-hydroxyfuran-2-sulfonamide (Pubchem CID 46175386) had the potential to be used as lead candidates against infections caused by K. pneumoniae producing NDM-1 strains.

bioinformatics↗

bioRxiv2025

Bisdemethoxycurcumin mitigates Alzheimer disease pathology through autophagy-mediated reduction of senescence and amyloid beta

AD pathology is accompanied by increased senescence and reduced levels of autophagy in the brain. We investigated whether pharmacologically inducing autophagy could alter the senescent phenotype and help ameliorate AD pathology. We discovered that Bisdemethoxycurcumin (BDMC), a natural compound found in Curcuma longa, stimulates autophagy in primary astrocytes. We found that autophagy and senescence exhibit an inverse relationship in aging astrocytes, with increased expression of senescent proteins and downregulation of autophagic proteins. However, treatment of aged astrocytes with BDMC reversed the senescent phenotype by ameliorating the impaired autophagy. Interestingly, the senescent phenotype persisted when autophagy was downregulated by knockdown of AMPK. Additionally, BDMC-induced autophagy aided in the removal of amyloid beta that was administered externally to the astrocytes. Further, to validate these results in a mouse model of AD, we confirmed that BDMC can significantly penetrate the blood-brain barrier (BBB) in mice. Therefore, we administered 50 and 100 mg/kg b.w. of BDMC to transgenic 3xTg-AD mice for two months. In their hippocampus, the Control 3xTg-AD animals showed more senescent cells and lower autophagy levels. In contrast, autophagic proteins were significantly upregulated while senescence indicators, such as senescence-associated secretory phenotype (SASP) proteins, were sharply downregulated in the brain of treated animals. Additionally, we discovered that the treated mices hippocampus had a significantly lower amyloid beta load. These molecular changes in the brain were ultimately reflected in the improved working memory and neuromuscular coordination behavior of mice treated with BDMC. This study warrants further evaluation of BDMC for the management of AD. Graphical Abstract O_FIG O_LINKSMALLFIG WIDTH=200 HEIGHT=139 SRC="FIGDIR/small/654834v1_ufig1.gif" ALT="Figure 1"> View larger version (53K): org.highwire.dtl.DTLVardef@1176bbforg.highwire.dtl.DTLVardef@a2e2cdorg.highwire.dtl.DTLVardef@1d824f5org.highwire.dtl.DTLVardef@1628a30_HPS_FORMAT_FIGEXP M_FIG This illustration was created by using biorender.com C_FIG

pharmacology and toxicology↗

bioRxiv2023

South Western Ghats: a niche of clove (Syzygium aromaticum (L.) Merr. & Perry) diversification

Survey conducted at major clove (Syzygium aromaticum (L.) Merr. & Perry) growing regions of South Western Ghats of India in the states of Kerala and Tamil Nadu identified thirty accessions with superior yield and distinct characters. Clove accessions were characterized based on twenty one qualitative and twelve quantitative traits. Variation among fifteen qualitative characters were found and the predominant traits observed were elliptical canopy shape, semi-erect branching pattern, lanceolate leaf lamina with acuminate apex, mid bud forming season, combination of 1,2,3,4,5 flower bud per cluster, medium sized bud, elliptical fruit and seed shape. Dendrogram constructed using the Unweighted Pair Group Method with Arithmetic Mean (UPGMA) method grouped thirty accessions into 5 major clusters at genetic similarity of 73%. Acc.19 was identified as a unique accession. Twelve quantitative characters were subjected to principal component analysis where three component groups were extracted, which explained 70.85 per cent of total variance. The score plot generated from the principal component loading grouped the accessions into 18 clusters. Minimal data set of four characters viz., plant height, canopy spread (EW), number of inflorescence per square meter and mature bud length was generated. Observation on the qualitative and minimum data set helps to identify the ideotypes. The geographical location was not found to influence genetic diversity. HighlightO_LIClove genotypes in South Western Ghats were surveyed and diversity identified C_LIO_LICombination of 1,2,3,4,5 flower bud per cluster was a unique character identified among cultivated clove C_LIO_LIMinimal data set of clove developed using plant height (m), canopy spread (EW), number of inflorescence per m2 and mature bud length (mm) C_LIO_LIIdeotype of clove developed C_LI

plant biology↗