Basavaraj Metikurki

In the present work, we synthesize 2-(4-allyl-2-methoxyphenoxy)-1-(4-phenylpiperazin-1-yl)ethan-1-one, a semisynthetic derivative of the natural product eugenol. The compound was synthesized via a three-step synthetic pathway involving esterification, hydrolysis, and subsequent coupling with 4-phenylpiperazine, as confirmed by FTIR, ¹H NMR, ¹³C NMR, and mass spectrometric data.

Glycogen synthase kinase-3 beta (GSK-3β) is a multifunctional serine/threonine kinase mediating multiple cellular functions, such as differentiation, apoptosis, and cell proliferation. Because of their ability to alter carcinogenic pathways, GSK-3β inhibitors are being explored for the development of anticancer molecules. In the present study, we synthesized and evaluated the cytotoxic properties of a series of twenty indole–triazole-linked pyrazolone derivatives, 10Aa–Ed. All derivatives were characterized by FTIR, ¹H/¹³C NMR, and high-resolution mass spectrometry (HRMS) methods. All compounds and standards, sunitinib and 5-Fluorouracil (5-FU), were screened against four adherent cell lines, including pancreatic adenocarcinoma (Capan-1), colorectal carcinoma (HCT-116), glioblastoma(LN229), and lung carcinoma (NCI-4460), and four non-adherent cell lines, including acute myeloid leukemia (HL-60), chronic myeloid leukemia (K562), T lymphoblast (MOLT4), and non-Hodgkin lymphoma (Z138). Among the screened derivatives, molecule 10Aa showed cytotoxicity against MOLT 4, Z138, and HL60 with CC₅₀ values of 14.45 μM, 15.34 μM, and 17.56 μM, respectively. GSK-3β kinase inhibition was evaluated with the 10Aa, which is capable of inhibiting GSK-3β in a dose-dependent manner. Additionally, molecular docking was performed to estimate the correlation between invitro data and GSK-3β binding affinity. The outcomes of the invitro experiments demonstrated strong concordance with the insilico data. The discovery yielded compounds 10Aa and 10Cd, which can be modified to create effective anticancer agents that target GSK-3β.

A series of 1,2,3-triazole-linked cyclic ketones (AR 1-14) were synthesized involving the condensation of triazole-aldehydes with cyclic ketones in tetrahydrofuran and potassium hydroxide. The synthesized derivatives were evaluated for their in vitro cytotoxicity against retinal (hTERT RPE-1)-1), pancreatic (Capan-1), myeloid (K-562, Hap-1), colorectal (HCT 116), lung (NCI-H460), lymphoblastic (DND-41) and non-Hodgkin lymphoma (Z-138) cells. Among the tested derivatives, compound 2,6-bis(4-((1-(4-fluorobenzyl)-1H-1,2,3-triazol-4-yl)-methoxy)benzylidene)cyclohexanone (AR-7) exhibited moderate cytotoxic property with an IC50 of 11.8 µM and 13.6 µM against pancreatic adenocarcinoma and colorectal carcinoma cells, respectively. Molecular docking against galectin-1 receptor (PDB ID: 4Y24) demonstrated a favourable binding interaction (-7.1 kcal/mol) indicating a strong receptor-ligand affinity.

Context: Traditional medicinal plant knowledge represents one of the oldest and most valuable contributions to the health sector of humanity. It serves as an essential guide to humans to develop better and healthier well-being. Medicinal plants possess phytoconstituents which exhibit enormous therapeutic effects. Aims: To evaluate the in vitro and in vivo anti-inflammatory activity of Macaranga peltata (MPCF) and Pongamia pinnata (PPEAF) fractions and estimate the phytochemicals responsible for their therapeutic action. Methods: Plant extracts and fractions were tested for their in vitro anti-inflammatory properties using the bovine serum albumin method and in vivo activity using the carrageenan-induced rat paw edema model. The selected fragments were analyzed for phytochemicals such as flavonoids, tannins, and total phenolics. Results: The extract yields indicate that P. pinnata contains non-polar compounds and M. peltata contains polar phytocompounds. Both the MPCF and PPEAF were found to contain flavonoids. However, MPCF also contained tannins and phenolic compounds that were found in lesser percentages in PPEAF. Conclusions: The chloroform fraction of M. peltata and ethyl acetate fraction of P. pinnata showed significant anti-inflammatory activity compared to the positive control group.

A series of 12 stilbene derivatives (23-34) were synthesized by reacting benzyl-triphenylphosphonium chlorides (9-14) and hydrochloride salt of 3,5-disubstituted-4-hydroxybenzaldehydes (21-22). The synthesized molecules were tested against the human breast cancer cell line MCF7 by 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) assay in 10% Dulbecco’s modified Eagle Medium (DMEM). Compound 23 exhibited significant cytotoxicity, with 1.11% viability at a concentration of 200 µM, compared to the reference standard resveratrol (15.14%) and 5-fluorouracil (51.86%). All the synthesized derivatives demonstrated equipotency to 5-fluorouracil (5-FU) at all the tested concentrations. The docking study was conducted on the tyrosine-protein kinase/Janus Kinase 2(JAK2) receptor using Autodock Vina. The results of the docking study suggest that, with the exception of compounds 29 (-6.7 kcal/mol) and 32 (-7.1 kcal/mol), most of the synthesized derivatives have exhibited glide scores greater than the standard resveratrol (-7.8 kcal/mol). This implies that these compounds 23-34 have a strong binding affinity to the JAK2 receptor, which is relevant in the context of cancer research, as JAK2 is associated with various signaling pathways involved in cell proliferation and survival.