Category: Medicinal Chemistry

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

The synthesis of new hybrid [1,2,4] triazolo [3,4-b][1,3,4]thiadiazine derivatives of imidazole (5a – 5m) and their structure determination using ¹HNMR, ¹³CNMR and mass spectral analysis were described. The in vitro cytotoxic activity of the compounds (5a – 5m) against three human cancer cell lines like MCF-7 and MDA-MB-231 (breast), alveolar (A-549) revealed that the compounds 5c, 5d, 5f, 5g, and 5m have shown greater activity against breast cancer cell lines than the remaining compounds. Compounds 5d and 5f have shown equipotent activity compared to the standard. In vitro tyrosine kinase EGFR inhibition assay for the same more potent compounds (5c, 5d, 5f, 5g, and 5m) revealed that 5f has more potent inhibiting power with an IC₅₀ value of 0.412±0.05 μM and 5d has equipotent inhibiting power with an IC₅₀ value of 0.436±0.07 μM compared to erlotinib (IC₅₀=0.423±0.03).

URN:NBN:sciencein.cbl.2023.v10.548

The expanding field of bioorthogonal chemistry has demonstrated significant potential in advancing reproductive medicine. This comprehensive review elucidates the multifaceted applications of bioorthogonal chemistry across various aspects of reproductive medicine, including gamete biology, energetics and metabolic regulations of gametes, targeted drug delivery, detection and therapeutic of endometriosis and polycystic ovarian syndrome (PCOS), developments of diagnostic tools and new management approaches to reproductive cancers. In gamete biology, bioorthogonal reactions enable the precise manipulation and tracking of biomolecules within gametes, thus facilitating a deeper understanding of gamete development, maturation, and interaction. Bioorthogonal chemistry also plays an indispensable role in deciphering the intricate energetics and metabolic regulations governing gamete function and competence, consequently fostering the development of novel therapeutic interventions. Targeted drug delivery, utilizing bioorthogonal click chemistry, can improve the specificity and efficacy of pharmacological treatments in reproductive disorders, such as endometriosis and PCOS. In the realm of reproductive diagnostics, bioorthogonal chemistry engenders innovative tools for sensitive and noninvasive detection of reproductive anomalies. Finally, the integration of bioorthogonal strategies in studying reproductive cancers can uncover new molecular targets for therapeutics, leading to more effective treatment modalities. Collectively, this review highlights the paramount importance of bioorthogonal chemistry in revolutionizing reproductive medicine and fostering breakthroughs in the comprehension and management of reproductive health.

URN:NBN:sciencein.cbl.2023.v10.545

Herein, synthesis of new Nilutamide-isoxazoles (5a-5n) via Cu(I)-promoted one-pot reaction between 1-(but-3-yn-1-yl)-5,5-dimethyl-3-(4-nitro-3-(trifluoromethyl)phenyl)imidazolidine-2,4-dione (3) and several aldehydes (4a-4n) in benign aq. ^tbutanol as key approach has been reported. The in vitro growth inhibition activity of all these compounds revealed that the majority of compounds were more active against DU-145 in comparison to PC3. Particularly, compounds 5f, 5h and 5k showed greater activity against DU-145 than the standard drug 5-Fluoro Uracil with IC₅₀ values <30 mM. whereas compound 5g showed comparable activity against DU-145 cell line with the positive control. The Epidermal growth factor receptor (EGFR) is well known to be expressed in DU-145 cancer cells, the most potent compounds 5f, 5h and 5k were then screened for their inhibitory potential against tyrosine kinase EGFR and found that compounds 5f and 5k showed remarkable inhibition with MIVs 93.4% and 91.3% respectively, while compound 5h displayed good inhibition (MIV = 84.6%) as compared to the Erlotinib.

URN:NBN:sciencein.cbl.2023.v10.542