Category: Medicinal Chemistry

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

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

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

Herein we synthesized new indole-thiazolidine-2,4-dione coupled isoxazoles (7a-n) via simple reactions like N-propargylation, Knoevenagel condensation and copper (I) catalysed one pot regioselective reactions. All the newly synthesized compounds were characterized by 1H-NMR, 13C-NMR and Mass spectra and they were screened for in vitro anticancer activity against three human cancer cell lines like A549 (lung), MCF-7 (breast), and SKOV3 (ovarian) using MTT assay and etoposide was used as the standard drug. As per the results the compounds 7e, 7f and 7g where shown selectivity towards A549 cell line with IC₅₀ values of 5.27 µM, 3.14 µM and 6.25 µM respectively and they are high active than etoposide. Further in vitro tubulin polymerization assay on three potent compounds (7e, 7f and 7g) revealed that compounds 7e and 7f have exhibited potency than standard combretastatin A-4 with IC₅₀ values 0.82 and .044 mM respectively.

URN:NBN:sciencein.cbl.2023.v10.531

Yucca gloriosa L. has been comprehensively assessed in vitro and in vivo for its action against asthma. Y. gloriosa L. is a rich source of phenolic compounds such as gloriosaols A-E and yuccaols A-E, which exhibit potent antioxidant activity. Gloriosaols A-E and yuccaols A-E are structurally related to corticosteroids. The current study describes the in silico docking of some important anti-asthmatic phytoconstituents from the plant Y. gloriosa L. with molecular targets of asthma. Toward the recognition of the binding methods of these pharmacologically dynamic components, molecular modelling studies were carried out with target proteins, i.e., interleukin (IL)-6 (1N26), IL-13 (3LB6) and TNF-α (2AZ5), using in silico molecular docking. The components demonstrated encouraging binding interactions with the amino acid residues at the active sites of these proteins, authenticating their verified efficiency as anti-asthmatic agents. The current research, in addition, provides insight into the possible herbal drug-receptor interaction and synthetic drug montelukast sodium receptor interaction, for the possible management of asthma.

URN:NBN:sciencein.cbl.2023.v10.509

Present investigation aimed to study the antimycobacterial potential of Mentha piperita essential oil fractions, identify its active constituents by GC-MS and preparation of nanoemulsion from biologically active fraction. Four oil fractions (R1, R2, R3, R4) were collected during hydrodistillation of Mentha piperiata leaves and tested in the two of mycobacterial strains by conventional disc diffusion method. Oil fractions R2 and R3 demonstrated maximum zone of inhibition of 39 mm and 36 mm in Mycobacterium smegmatis, 33 mm and 31 mm in Mycobacterium bovis BCG respectively at a dilution of 75% in DMSO compared to standard drug isoniazid (23 mm in 4 µg/ml). GC-MS analysis of the most active fraction R2 reveals the presence of menthol (70.69%), isomenthone (14.63%) and neomenthol (6.82%) as major constituents. To enhance bioavailability of oil fraction, the nanoemulsions were prepared from R2 by sonication method. Nanoemulsions, N1 and N2 prepared by varying surfactant concentrations were tested in Mycobacterium bovis BCG using quantitative and colorimetric resazurin microtiter assay (REMA). Nanoemulsions, N1 and N2 have shown 97-100 % bacterial growth inhibition at 3.125 % concentration in the culture medium compared with the culture control.

URN:NBN:sciencein.cbl.2023.v10.507