Remodeling of membrane lipid homeostasis in azole resistant isolates of Candida albicans

Remodeling of membrane lipid homeostasis in azole resistant isolates of Candida albicans

Azole resistance mechanisms in Candida albicans infections majorly focus around the alteration of target enzymes, overexpression of efflux pump proteins, and changes in lipid metabolism. Our earlier lipidomic studies have linked changes in cellular lipid compositions to drug susceptibilities and phenotypic defects. This study investigates the relationship between whole cell and membrane lipid profiles in isogenic drug-susceptible and resistant isolates of C. albicans. We have examined the fatty acid and sterol snapshot lipidomics in whole cells, plasma membrane, and lipid rafts. Correlations were discovered between these lipid compositions and the observed drug resistance in C. albicans. Although the correlations drawn from cellular and plasma membrane data corroborate, understanding plasma membrane and suborganellar (rafts in this case) lipid changes may provide better insights into their roles in efflux pump activities and localization, and drug susceptibilities.

URN:NBN:sciencein.cbl.2024.v11.658

Remodeling of membrane lipid homeostasis in azole resistant isolates of Candida albicans – https://pubs.thesciencein.org/journal/index.php/cbl/article/view/a658

Chemical Biology Letters

The ScienceIn Conference Fellowship

The fellowship for attending the National and International Science conferences and symposium in India.

The ScienceIN offers fellowship to support the scholars for attending the national and international science conferences and symposium in India. The ‘Conference Fellowship’ from The ScienceIN covers the full registration fee of participants (preferably young researchers – Ph.D. students, Research Associates, PDFs, and young faculty/scientists) via either waive off (for future sponsored conferences) or refund (already completed conferences).

At present 50 Conference Fellowships are available for the participants of the

CRSI – National Symposium in Chemistry – 32 held at BITS Pilani, Pilani 2-4 Feb 2024.

who are authors of either ‘Journal of Molecular Chemistry‘ and/or ‘Molecular Letters‘ .

The participants of the CRSI-NSC-32 can claim the refund of their registration fee (full – excluding other fee, if any) if they have published any article in JMC or ML (or can publish an article in JMC or ML before the last date (i.e. 31-Oct-24) for claim).
– Submit your registration fee slip (snap or online transfer details) and title of published article (JMC/ML) to the pubs@thesciencein.org for refund.
– Provide the bank details/upi id for online refund of your registration fee (the fellowship will be directly credited in Scholar’s account).
– One author from respective article will be eligible for refund.
– Articles published or accepted for publication before the last date of claim (31-Oct-2024) will be eligible of this fellowship.
– First come first served will be the process for disbursing the fellowships.
– It is for Indian Scholars only (fellowship in INR will be credited).

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All future announcements related to Conference fellowships will be on this page, scholars can visit this page for open fellowships for attending the science conference.

Design, synthesis and biological evaluation of novel sulfamoyl benzamides as allosteric activators of human glucokinase

Design, synthesis and biological evaluation of novel sulfamoyl benzamides as allosteric activators of human glucokinase

Glucokinase (GK) activators, which target the GK enzyme, are an emerging class of therapeutics with promising effects against diabetes. The objective of this work was to create a new group of sulfamoyl benzamide derivatives with the ability to activate GK and evaluate their effectiveness in treating diabetes. From benzoic acid, several compounds containing sulfamoyl benzamide scaffold were synthesized and evaluated for their ability to activate GK in an in vitro enzymatic experiment. In silico docking analyses were employed to explore how the most suitable arrangements in the allosteric area of the GK enzyme interact during binding. The effectiveness of the identified substances in reducing high blood sugar levels was assessed using the oral glucose tolerance test (OGTT) in healthy rats. This evaluation was based on the results of laboratory tests on enzymes and in silico simulations. One of the most active compounds from the antihyperglycemic assay was then tested for its antidiabetic effects in an induced diabetic rat OGTT assay. The in vitro GK activation was best among compounds 1, 6, and 8 (activation fold: 2.03-2.09). In the OGTT assay (normal rats), compounds 1 and 6 showed promising antihyperglycemic activity. In vivo antidiabetic assay confirmed the consistency with in silico and in vitro outcomes. The newly synthesized derivatives of sulfamoyl benzamide have the potential to be used as a basis for the development of further GK activators that are both safe and efficacious and can be administered orally. These activators may be used as therapeutic agents to treat type 2 diabetes.

URN:NBN:sciencein.cbl.2024.v11.657

Design, synthesis and biological evaluation of novel sulfamoyl benzamides as allosteric activators of human glucokinase – https://pubs.thesciencein.org/journal/index.php/cbl/article/view/a657

Chemical Biology Letters

Molecular pathways with role to play in oral cancer: A mini-review

Molecular pathways with role to play in oral cancer: A mini-review

Oral cancer is the sixth most prevalent type of cancer worldwide and third in India out of the different cancer types identified. Mouth and oral cancers collectively refer to cancers of the buccal cavity, lips, oropharynx, hypopharynx, and larynx. Genetic anomalies, the upregulation of several proteins, the deregulation of tumor-suppressive and oncogenes, and risk factors like alcohol and tobacco consumption are a few examples of the known irregularities that contribute to the development of oral cancer through the accumulation of various carcinogenic substances. Oral cancer is caused and developed by multiple molecular and cellular pathways such as PI3K/AKT/mTOR, Ras-Raf-MEK-ERK pathway, Wnt signaling, NF-κB pathway, Hippo pathway, etc. In addition, various genes including TP53, PTEN, CDKN2A, HRAS, PIK3CA, NOTCH1, IRF6, TP63, etc. are also involved in this malignancy. Therefore, it is crucial to have a deep understanding of these pathways to properly understand the development of oral cancer. This short review focuses on compiling together various signaling and molecular pathways accountable for oral carcinoma development.

URN:NBN:sciencein.cbl.2024.v11.652

Molecular pathways with role to play in oral cancer: A mini-review – https://pubs.thesciencein.org/journal/index.php/cbl/article/view/a652

Chemical Biology Letters

Synthesis of Indole-Oxadiazole coupled isoxazole hybrids as potent EGFR targeting anticancer agents

Synthesis of Indole-Oxadiazole coupled isoxazole hybrids as potent EGFR targeting anticancer agents

The synthesis of new indole-oxadiazole coupled isoxazole hybrids (6a–o) synthesized by the Cu(I)-catalyzed reaction of in situ generated nitrile oxides with 3-(3,5-dichloro-4-methoxyphenyl)-5-(1-(prop-2-yn-1-yl)-1H-indol-3-yl)-1,2,4-oxadiazole in good yields have been reported here. The chemical structures of all newly synthesized hybrids were confirmed by 1H-NMR, 13C-NMR, and Mass spectra. All synthesized compounds were screened for their in vitro cytotoxicity against two breast cancer cell lines MCF-7 and MDA-MB-231 respectively. All the derivatives were more active against MCF7 than MDA-MB-231 cancer cells and few compounds showed better activity than the standard erlotinib. The ability of more potent compounds to inhibit EGFR tyrosine kinase, one of the key enzymes involved in breast carcinomas was evaluated by in vitro enzymatic assay and it was found that the compound (6g) and (6m) had more inhibitory activity IC50 values 0.311±0.05 and 0.203±0.03 mM than erlotinib (IC50=0.421±0.03 mM).

URN:NBN:sciencein.cbl.2024.v11.651

Synthesis of Indole-Oxadiazole coupled isoxazole hybrids as potent EGFR targeting anticancer agents – https://pubs.thesciencein.org/journal/index.php/cbl/article/view/a651

Chemical Biology Letters

Impact of resistin gene polymorphism on insulin resistance and Type 2 diabetes in Iraqi Babylon province patients

Impact of resistin gene polymorphism on insulin resistance and Type 2 diabetes in Iraqi Babylon province patients

Resistin is cysteine-rich polypeptide produced by adipocytes and macrophages. This study aims to assess the role of resistin and its gene polymorphisms (rs-34861192 G>A, NG-023447 C>G) as potential link between obesity and insulin resistance in the development of T2DM. Blood samples were collected from 120 participants (60 control are divided into 30 normal weight and 30 obese without T2DM) and (60 patients of Type 2 dm DM) are divided into 30 normal weight and 30 obese). Resistin and insulin levels were increased significantly in the patients’ group (p<0.05). Gene analysis indicated that rs-34861192 was associated significantly (P<0.01) with T2DM in dominant, recessive, and co-dominant models. The rs-34861192 AA genotype showed a significant difference in normal-weight and obese T2DM compared to control (P<0.001) only. The significant difference of GG genotype in normal-weight patients than control exclusively. In the diabetic patients, mutant genotype (AA) of rs34861192 was associated with circulating resistin level. The expression of retn gene was high. Genotype AA of rs- 34861192 was correlated positively with folding change. Mutant AA of rs-34861192 G>A plays an important role in development of T2DM through its effect on resistin levels in the circulation that considered as a major factor for developing T2DM.

URN:NBN:sciencein.cbl.2023.v10.629

Impact of resistin gene polymorphism on insulin resistance and Type 2 diabetes in Iraqi Babylon province patients – https://pubs.thesciencein.org/journal/index.php/cbl/article/view/a629

Chemical Biology Letters

Synthesis of 1,4-disubstituted-1,2,3-Triazole derivatives for investigation of inhibition and molecular docking studies against Xanthine Oxidase

Synthesis of 1,4-disubstituted-1,2,3-Triazole derivatives for investigation of inhibition and molecular docking studies against Xanthine Oxidase

This study evaluates the inhibition effect of new 1,4-disubstituted-1,2,3-triazoles against Xanthine Oxidase supplemented by molecular modelling. Nine compounds of 1,4-disubstituted-1,2,3-triazoles by Sharpless’s approach have been synthesized in this report. The structures of the synthesized compounds were characterized using FT-IR, 1H and 13C-NMR and Mass spectroscopies Among these synthesized molecules (5-bromothiophen-2-yl)(1-(3-fluorobenzyl)-1H-1,2,3-triazole-4-yl)methanone (9f) and (5-Bromothiophen-2-yl(1-(4-methoxybenzyl)-1H-1,2,3-triazole-4-yl)methanone (9h) showed better activity against Xanthine oxidase (XO) compared to allopurinol. In the light of the XO inhibition results, triazoles having of ketone moiety (9f-i) were found to be more active than triazoles of ketone-free (9a-e). These results were supported by docking models. The docking calculations of the target XO with nine available compounds showed good binding energies with favourable binding interactions. These findings were particularly evident that 9f (BE -7.29 kcal/mol) and 9h (BE -7.59 kcal/mol) are represented encouraging higher inhibition properties towards xanthine oxidase (XO), compared to allopurinol as a reference compound. Significant binding energies and interactions obtained by performing the docking studies are demonstrated, in particular, that the compounds 9f and 9h may be more potential bio compounds than the positive compounds, allopurinol, and febuxostat.

URN:NBN:sciencein.cbl.2023.v10.628

Synthesis of 1,4-disubstituted-1,2,3-Triazole derivatives for investigation of inhibition and molecular docking studies against Xanthine Oxidase – https://pubs.thesciencein.org/journal/index.php/cbl/article/view/a628

Chemical Biology Letters

Synthesis of novel phthalimide-based piperazine conjugated analogs as anti-malarial agents

Synthesis of novel phthalimide-based piperazine conjugated analogs as anti-malarial agents

In the present report, we synthesized twelve novel phthalimide analogs and evaluated for antiplasmodial efficacy on Plasmodium falciparum culture. Two molecules exhibited significant inhibition percentages at 1 µM concentration without any apparent cytotoxicity on HepG2 cells. Inhibitory concentration (IC50) for both the hit compounds 6d and 8a was observed in micromolar range, 1.20 µM and 1.66 µM, respectively. Extensive in silico studies conducted indicate plasmepsin IX as a possible target for inhibitory activity of the reported molecules.

URN:NBN:sciencein.cbl.2023.v10.627

Synthesis of novel phthalimide-based piperazine conjugated analogs as anti-malarial agents – https://pubs.thesciencein.org/journal/index.php/cbl/article/view/a627

Chemical Biology Letters

Small-molecules against Oxidative stress mediated Neurodegenerative diseases

Small-molecules against Oxidative stress mediated Neurodegenerative diseases

Neurodegenerative diseases, marked by the gradual deterioration of neuronal structure and function, impose a significant burden on global healthcare systems. Oxidative stress, resulting from an imbalance between reactive oxidant production and cellular antioxidant defense, is believed to play a significant role in the development of various neurodegenerative disorders, including Alzheimer’s disease, Parkinson’s disease, and Huntington’s disease. Recently, there has been a growing interest in exploring small compounds as potential therapeutic agents to counteract oxidative stress. In addition to highlighting the potential of small molecules to prevent oxidative stress-mediated neuronal damage, this article provides an overview of the function of oxidative stress in neurodegenerative illnesses. Targeting numerous oxidative stress-related pathways, a number of small molecules, including both natural and synthetic antioxidants, have shown promise for neuroprotective benefits. These substances neutralise reactive oxidants, boost endogenous antioxidant defences, reduce inflammation, alter mitochondrial function, and encourage neurotrophic growth.

URN:NBN:sciencein.cbl.2023.v10.626

Small-molecules against Oxidative stress mediated Neurodegenerative diseases – https://pubs.thesciencein.org/journal/index.php/cbl/article/view/a626

Chemical Biology Letters

Molecular links between metabolome and epigenome: AMPK-TET2 signalling pathway and their natural activators

Molecular links between metabolome and epigenome: AMPK-TET2 signalling pathway and their natural activators

Emerging evidence suggests that sustained diabetes-associated factors such as inflammation, hyperinsulinemia, and hyperglycemia are major contributors to aberrant cell proliferation and subsequent neoplastic transformation. Epidemiological studies have also highlighted that diabetes promoting a sedentary lifestyle, with or without the direct involvement of insulin, is frequently linked to cancer. However, our knowledge regarding the molecular mechanisms that correlate hyperglycemia to oncogenic transformations remains limited. In this regard, a recent study has proved that hyperglycemia inactivates AMPK, destabilizing the TET2 and its tumour-suppressive role and ultimately predisposing diabetes mellitus patients to cancer. We must explore a reverse pharmacology-based ethnopharmacological approach to managing hyperglycemia associated with oncogenesis. Botanical-derived natural products have greater structural and functional diversity with fewer or no side effects on humans. The present review discusses the molecular relationship between hyperglycemia and cancer progression and the impact of natural products as therapeutic agents on the hyperglycemia-cancer-associated signaling pathway.

URN:NBN:sciencein.cbl.2023.v10.552

Molecular links between metabolome and epigenome: AMPK-TET2 signalling pathway and their natural activators – https://pubs.thesciencein.org/journal/index.php/cbl/article/view/a552

Chemical Biology Letters