Category: Medicinal Chemistry

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

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

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

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

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

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

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

Type 1 diabetes is a heterogeneous disorder caused by reduced β-cell mass as a result of T-cell mediated autoimmune destruction. C-peptide is a linker chain cleaved from proinsulin to produce the mature, functional insulin hormone. Irisin is a novel adipo-myokine plays a crucial role in glucose homeostasis regulation. Preptin is a peptide hormone synthesized in β-cells and plays a role in augmenting insulin secretion. The current study aims to investigate preptin and irisin levels in diabetic children and determine their correlation with C-peptide and the development of this disease. This study recruited 90 children, divided into two groups: 45 patients and 45 controls. Commercial ELISA kits were used to measure C-peptide, irisin, and preptin. C-peptide levels were significantly decreased among the patients’ group (P<0.05). Preptin and irisin levels were significantly increased in the patients’ group (P<0.05). C-peptide was noticeably correlated with preptin, irisin and RBS (P <0.05). Preptin and irisin levels also had a positive correlation with RBS (P<0.05). In regression analysis, irisin had a strong association with C-peptide. In conclusion, irisin was a considerable predictive marker for the residual β-cells through its association with preptin and C-peptide in regression analysis. Preptin might be an indicator of insulin resistance.

URN:NBN:sciencein.cbl.2023.v10.551

Chemical composition and additive inhibitory activity of combination of Mentha piperita, Cinnamonum vernum & Jasminum officinale essential oils as an alternative therapy against Dermatophytosis

The antifungal potential of Peppermint, Cinnamon & Jasmine essential oils alone and in combination, against common causes of superficial fungal infections in humans was investigated via in-vitro investigations, in order to determine a suitable dosage for use in clinical trials. Antimycotic activity of three plant derived Essential oils (EOs) namely Mentha piperita, Cinnamonum vernum & Jasminum officinale were evaluated against Trichophyton equinum and Microsporum canis, causative agent of zoonotic dermatophytosis by Disc diffusion method alone and in mixture and further determination of Minimum Inhibitory Concentration (MIC) by modified Microdilution method. Chemical compositions of M.piperita, C.vernum & J. officinale essential oil were determined by Gas chromatography Mass spectrometry (GC-MS). In M.piperita essential oil, thirteen compounds, C.vernum, ten compounds and J. officinale, fifteen compounds were identified by GC-MS. The excellent antidermatophytic activity of mixture of oils was found against M.canis & T.equinum as compared to single oils and standard drugs used. The results concluded that the combination of three essential oils showed remarkable and excellent inhibitory activity against fungal pathogens and can be used as an alternative topical therapy for the treatment of dermatophytosis after undergoing clinical trials and also regarded as an environmentally safe mode of diseases control.

URN:NBN:sciencein.cbl.2023.v10.550