Category: Medicinal Chemistry

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

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

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.

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

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

Targeting of epidermal growth factor receptors (EGFRs) and vascular endothelial growth factor receptors (VEGFRs) has become a major strategy for the control of head and neck cancer. c-MET, a receptor tyrosine kinase is known to be expressed in many cancers including the head and neck squamous cell carcinoma (HNSCC). The c-MET activity has been correlated with many signaling pathways that help the cancer cells to proliferate, migrate and invade into the normal, healthy tissues. The association of c-MET with glycolytic pathway in HNSCC has not been elucidated yet. Since, increased glycolysis has emerged as a major hallmark for cancer cell proliferation, targeting c-MET could bring an impact to inhibit HNSCC progression. In the present study we use various In-silico tools available to identify the association of c-MET with the major metabolic genes such as HK-II (Hexokinase-II), GLUT-1 (Glucose transporter-I), LDH-A (Lactate dehydrogenase-A), PFK-II (Phosphofructokinase-II) and MCT-1 (Monocarboxylate transferase-1) in HNSCC patient datasets available from The Cancer Genome Atlas (TCGA). Protein networking analysis was used to determine the correlation of c-MET with the metabolic genes. Retrieved sequenced data pathway analysis gives the network of genes associated in the activation of glycolytic pathway. Gene ontology and Enrichr studies provide an insight into c-MET activity in metabolism through molecular, functional and pathway basis in HNSCC. Furthermore, we also have shown a negative correlation of c-MET with immune cell infiltration, suggesting c-MET might have a role in immune suppression in HNSCC patients. Further validation on this study could possibly make c-MET as a potential target to inhibit HNSCC.

URN:NBN:sciencein.cbl.2023.v10.532