Design, Synthesis and In-Silico Studies of Piperidine-Dihydropyridine Hybrids as Anticancer Agents.

In this study, we designed, synthesized and characterized a novel series of piperidine-dihydropyridine hybrid compounds and characterized them by 1H-NMR, 13C NMR, mass spectrometry (MS), and elemental analysis. Subsequently, we assessed their in vitro anticancer potentials against the human breast adenocarcinoma cell line MCF-7 and the lung cancer cell line A-549. Several of these compounds demonstrated significant activity, with IC50 values ranging from 15.94 µM to 48.04 µM for A-549 and 24.68 µM to 59.12 µM for MCF-7, when compared to the reference drug Cisplatin.Notably, a compound featuring a 3-fluoro substitution in the carboxamide series exhibited robust inhibitory effects, with an IC50 of 15.94±0.201 µM against A-549 cells and an IC50 of 22.12±0.213 µM against MCF-7 cells, respectively. Additionally, a compound containing a cyclobutyl ring displayed potent activity, with an IC50 of 16.56±0.125 µM against A-549 and an IC50 of 24.68±0.217 µM against MCF-7 cells, respectively. Furthermore, molecular docking studies against the Epidermal Growth Factor Receptor (EGFR) (PDB ID: 2J6M) revealed favourable binding scores and interactions, suggesting their potential as promising candidates for further investigation in the context of anticancer drug development.

Cu-Catalyzed Tandem C-N and C-C Bond Formation Leading to 4(1H)-Quinolones: A Scaffold with Diverse Biological Properties from Totally New Raw Materials in a Single Step.

A novel Cu-catalyzed tandem C-N and C-C bond-formation reaction has been developed to furnish 2-substituted-4-(1H)-quinolones. 4-(1H)-quinolones play an important role in medicinal chemistry. Many 2-aryl(alkyl)-4(1H)-quinolones are found to exhibit diverse biological properties. While traditional methods have inherent issues [like starting materials with incompatible functional groups (NH2 and keto groups)], many modern methods either require activated starting materials (like Ynones) or employ expensive metals (Pd, Rh, Au, etc.) involving carbonylation using CO or metal complexes. Our protocol presents an environmentally friendly one-step method for the construction of these useful 2-substituted-4-(1H)-quinolones from easily available aryl boronic acid (or pinacolate ester) and nitriles as new raw materials, using a cheap Cu-catalyst and O2 (air) as a green oxidant. We further extended its application to the synthesis of various natural products, including the first formal total synthesis of punarnavine. A plausible mechanism involving an aryl nitrilium ion (formed due to the intermolecular C-N bond-forming coupling between aryl boron species and the nitrile group) followed by tandem intramolecular C-C bond formation has been proposed.

One-Pot Synthesis of Chromone-2-carboxylate Scaffold: An Important Pharmacophore with Diverse Biological Properties.

Chromone-2-carboxylate scaffold is growing as an important pharmacophore in medicinal chemistry with diverse biological properties. We have developed a facile one-pot transformation of 2-fluoroacetophenone directly to chromone-2-carboxylate scaffold in a single step via a tandem C-C and C-O bond formation. The majority of the previously reported medicinal chemistry synthetic protocols primarily used only one procedure which follows a two-step strategy that needs to start with "2-hydroxyacetophenone". Our methodology not only serves as an alternative one-pot methodology but also allows chemists to start from different raw materials (2-fluoroacetophenone) other than the traditional ortho-hydroxyacetophenone for maintaining the regioselectivity in the cyclization step. We further demonstrated the utility of our protocol by successfully extending the application to the synthesis of two natural products (Halenic acids A and B), various bis-chromones including drug molecules (DSCG, cromoglicic acid), and potent anti-Alzheimer compound (F-cromolyn). This methodology can serve as a promising alternative tool for finding new bioactive chromones with diverse modifications due to the opportunity to use new raw materials in the synthesis of chromones.

Design, Synthesis and Biological Evaluation of Novel Urea and Thiourea Bearing thieno[3,2-d]-pyrimidines as PI3 Kinase Inhibitors.

BACKGROUND: Phosphatidylinositol-3-kinase α (PI3Kα) is a ubiquitous intracellular enzyme, mainly involved in intracellular signaling pathways, promotes cellular growth, proliferation, and differentiation. Therefore, inhibition of PI3K can be a hotspot in molecular targeted therapy for the treatment of cancer. METHODS: The present research work involves molecular docking studies performed to screen derivatives of urea and thiourea bearing thieno [3,2-d]-pyrimidines against the active site of PI3K enzyme using MOE.2008.10. The designed structures (6a-f) and (7a-j) were synthesized by the facile synthetic methods and evaluated for their anticancer activity against HT-29 and MCF-7 cell lines and inhibitory activity against PI3Kα enzyme. RESULTS: Among the tested compounds, 4-(4-(2-(3-(pyrimidin-2-yl)thioureido)ethyl)piperazin-1-yl)thieno[3,2- d]pyrimidine-6-carboxamide (7f) showed the highest anticancer activity against HT-29 and MCF-7 cell lines with IC50 values of 2.18 µM and 4.25 µM, respectively. Further, the same compound also exhibited potent PI3Kα inhibitory activity with IC50 value of 1.26 µM. CONCLUSION: Docking studies supported the initial pharmacophoric hypothesis and suggested a mode of interaction at the active binding site of PI3Kα, demonstrating that the target compounds were potential inhibitory agents for cancer therapy.

Design, synthesis, in silico and in vitro evaluation of thiophene derivatives: A potent tyrosine phosphatase 1B inhibitor and anticancer activity.

A series of novel methyl 4-(4-amidoaryl)-3-methoxythiophene-2-carboxylate derivatives were designed against the active site of protein tyrosine phosphatise 1B (PTP1B) enzyme using MOE.2008.10. These molecules are also subjected for in silico toxicity prediction studies and considering their corresponding drug scores, it implied that, the molecules are promising as anticancer agents. The designed compounds were synthesized by using suitable methods and characterized. They were subjected to inhibitory activity against PTP1B and in vitro anticancer activity by MTT assay. Most of the tested compounds showed potent inhibitory activity against PTP1B, among the compounds tested, compound 5b exhibited the highest activity (IC50=5.25µM) and remarkable cytotoxic activity at 0.09µM of IC50 against the MCF-7 cell line. In addition to this, compound 5c also showed potential anticancer activity at 2.22µM of IC50 against MCF-7 and 0.72µM against HepG2 cell lines as well as PTP1B inhibitory activity at IC50 of 6.37µM.