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

Association of C-peptide with novel hormones in children with type 1 diabetes: A rising potentials for more reliable biomarkers.

Association of C-peptide with novel hormones in children with type 1 diabetes: A rising potentials for more reliable biomarkers.

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

Association of C-peptide with novel hormones in children with type 1 diabetes: A rising potentials for more reliable biomarkers. – https://pubs.thesciencein.org/journal/index.php/cbl/article/view/a551

Chemical Biology Letters

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

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

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

– https://pubs.thesciencein.org/journal/index.php/cbl/article/view/626

Chemical Biology Letters

Synthesis of novel imidazolo-[1,2,4]triazolo[3,4-b][1,3,4]thiadiazine hybrids as in vitro EGFR inhibitors

Synthesis of novel imidazolo-[1,2,4]triazolo[3,4-b][1,3,4]thiadiazine hybrids as in vitro EGFR inhibitors

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

Synthesis of novel imidazolo-[1,2,4]triazolo[3,4-b][1,3,4]thiadiazine hybrids as in vitro EGFR inhibitors – https://pubs.thesciencein.org/journal/index.php/cbl/article/view/a548

Chemical Biology Letters

Bioorthogonal chemistry in the reproductive medicine

Bioorthogonal chemistry in the reproductive medicine

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

Bioorthogonal chemistry in the reproductive medicine – https://pubs.thesciencein.org/journal/index.php/cbl/article/view/a545

Chemical Biology Letters

Anti-prostate cancer and anti-EGFR activities of new Nilutamide-isoxazole hybrids

Anti-prostate cancer and anti-EGFR activities of new Nilutamide-isoxazole hybrids

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

Anti-prostate cancer and anti-EGFR activities of new Nilutamide-isoxazole hybrids – https://pubs.thesciencein.org/journal/index.php/cbl/article/view/a542

Chemical Biology Letters

Novel fluorinated piperazine based-amino acid derivatives as antiplasmodial agents: Synthesis, bioactivity and computational studies

Novel fluorinated piperazine based-amino acid derivatives as antiplasmodial agents: Synthesis, bioactivity and computational studies

A library of twenty novel analogues of fluorinated, N-(3-hydroxy-1-phenyl-4-(4-phenylpiperazin-1-yl)alkyl)amides containing different amino acids were synthesized and tested for the activity against Plasmodium falciparum (Pf3D7) culture. All the tested compounds showed TC50 values >100 µM on HepG2 cells. Hit analogues 12c and 12e, displayed IC50 values in the sub-micromolar range, i.e., 0.696±0.0462 µM and 0.9377±0.0461 µM, respectively. Compounds 12c and 12e were also evaluated in combination with artemisinin, which slightly improved the activity of both the compounds with IC50 values of 0.19 µM and 0.26 µM, respectively. For compounds 12c and 12e, in-silico studies were carried out. Overall, results obtained from both in vitro and in-silico studies, indicated that 12c and 12e were hit compounds with maximum potency.

URN:NBN:sciencein.cbl.2023.v10.543

Novel fluorinated piperazine based-amino acid derivatives as antiplasmodial agents: Synthesis, bioactivity and computational studies – https://pubs.thesciencein.org/journal/index.php/cbl/article/view/a543

Chemical Biology Letters

Dietary Polyphenolics: Mechanistic role in control management of Diabetes and Metabolic Syndrome

Dietary Polyphenolics: Mechanistic role in control management of Diabetes and Metabolic Syndrome

The search for an antidiabetic drug is going on three fronts: technological (for instance, development of an artificial pancreas), biological (such as pancreas and islet cell transplants), and pharmacological. Our review focusses on the role of polyphenolics in pharmacological research for T2DM. Being the most abundant antioxidants in human diets, dietary polyphenols have proven efficacy against a variety of diseases in both animal and human trials. Here, the authors present a review of advances in using polyphenols obtained from diet against diabetes and metabolic syndrome. Authors have discussed the role of polyphenols in disease management, and their sources. In addition to that, current knowledge of prevalent pathways of their action in cases of diabetes and metabolic syndrome have been discussed. The future directions and perspectives about diet polyphenols as a good alternative to first-line drug interventions have been included.

Dietary Polyphenolics: Mechanistic role in control management of Diabetes and Metabolic Syndrome – https://pubs.thesciencein.org/journal/index.php/cbl/article/view/a541

Chemical Biology Letters

Role of Acetylcholinesterase (AChE) reactivators in the treatment of Organophosphorus poisoning: in vivo, in vitro, and in silico studies

Role of Acetylcholinesterase (AChE) reactivators in the treatment of Organophosphorus poisoning: in vivo, in vitro, and in silico studies

Chemical warfare agents, especially organophosphorus (OP) compounds, are known for their extreme toxicity causing inhibition of acetylcholinesterase (AChE) enzyme activity due to covalent phosphorylation. This leads to functional impairment of muscarinic nicotinic acetylcholine receptors, resulting in severe ill effects that ultimately lead to death. For OP poisoning, AChE reactivators play a crucial role in the treatment process. Among several AChE reactivators, Oxime reactivators are majorly employed for the treatment of OP intoxication, nevertheless, these are associated with certain drawbacks such as their toxic effects, low blood-brain barrier (BBB) penetration, less reactivation in the central nervous system (CNS), and inefficiency toward all nerve agents, and blocked AChE. As a result, new therapeutic strategies are required. Recent attempts are focused on the design and synthesis of uncharged oximes or non-oxime reactivators which can overcome the limitations of oxime-based reactivators. A novel class of non-oxime reactivators is gaining interest, including compounds like Mannich phenols, chloroquines, and some general bases. This review is a novel attempt to incorporate various possible oxime and non-oxime AChE reactivators for OP intoxication along with their in vitro, in vivo, and in silico studies.

URN:NBN:sciencein.cbl.2023.v10.538

Role of Acetylcholinesterase (AChE) reactivators in the treatment of Organophosphorus poisoning: in vivo, in vitro, and in silico studies – https://pubs.thesciencein.org/journal/index.php/cbl/article/view/538

Chemical Biology Letters

In-vitro evaluation of synergism in antioxidant efficiency of Quercetin and Resveratrol

In-vitro evaluation of synergism in antioxidant efficiency of Quercetin and Resveratrol

Plants serve as an excellent source of therapeutic molecules that help in medicinal treatments. The production of large amounts of pure phytocompounds from plant sources for human consumption and the nature of phytocompounds exhibiting toxicity issues at higher dosages lead to the challenge of increasing the therapeutic effect by using low dosages. This current study focuses on extracting two active antioxidant compounds, quercetin (Q) and resveratrol (R), from plant sources and evaluating their ability to exhibit antioxidant synergism through in vitro models. Quercetin and resveratrol were extracted using an ethanol-solvent extraction procedure from Allium cepa, and Vitis vinifera peels, respectively. The extracts were subjected to qualitative and quantitative analysis, column chromatography and then High-Performance Liquid chromatography for purification. DPPH, ABTS+, SOS, and cellular antioxidant assays evaluated the synergistic antioxidant activity of the quercetin and resveratrol complex. The results showed synergistic antioxidant efficacy values approximately as follows: 5.37 % in DPPH, 15.26 % in ABTS+, 11.99 % in SOS, and 19.13 % in cellular antioxidant assays when both molecules were used combinedly. The results promisingly pave the way for a new dimension in nutraceuticals formulation parameters which could trigger combined molecular usage to achieve better results at low dosages.

URN:NBN:sciencein.cbl.2023.v10.534

In-vitro evaluation of synergism in antioxidant efficiency of Quercetin and Resveratrol – https://pubs.thesciencein.org/journal/index.php/cbl/article/view/534

Chemical Biology Letters