Design, synthesis, graph theoretical analysis and molecular modelling studies of novel substituted quinoline analogues as promising anti-breast cancer agents.

The most promising class of heterocyclic compounds in medicinal chemistry are those with the quinolin-2-one nucleus. It is a versatile heterocyclic molecule that has been put together with numerous pharmaceutical substances and is crucial in the creation of anticancer medications. In this view, the present research work deals with design, synthesis, and characterization of various analogous of quinolin-2-one nucleus and evaluation of their anticancer activity against MCF-7 cells (adenoma breast cancer cell line). Fourteen new compounds have been synthesised using suitable synthetic route and are characterized by FTIR, 1H NMR, 13C NMR and Mass spectral data. Molecular docking studies of the title compounds were carried out using PyRx 0.8 tool in AutoDock Vina program. All the synthesised compounds were exhibited well conserved hydrogen bonding with one or more amino acid residues in the active pocket of EGFR tyrosine kinase (PDB ID: 1m17). The docking score of the derivatives ranged from - 6.7 to - 9.5 kcal mol-1, standard drug Imatinib with - 9.6 kcal mol-1 and standard active ligand 4-anilinoquinazoline with - 7.7 kcal mol-1. The designed compound IV-A1 showed least binding energy (- 9.5 kcal mol-1) against EGFR tyrosine kinase receptor. Further, top scored compound, IV-A1 found to be most significant against MCF-7 cells with IC50 value of 0.0870 µM mL-1, TGI of 0.0958 µM mL-1, GI50 of 0.00499 µM mL-1, LC50 of 1.670 µM mL-1.

A Recent Advancement in Nanotechnology Approaches for the Treatment of Cervical Cancer.

BACKGROUND: Cervical cancer is one of the leading causes of female death, with a mortality rate of over 200,000 per year in developing countries. Despite a decrease in cervical cancer occurrences in developed countries over the last decade, the frequency of the disease in developing nations continues to rise at an alarming rate, particularly when it is linked to the human papillomavirus (HPV). With just a few highly invasive conventional therapies available, there is a clear need for novel treatment options such as nanotechnology-based chemotherapeutic drug delivery. METHODS: Traditional anticancer therapy is limited by poor drug potency, non-specificity, unwanted side effects, and the development of multiple drug resistance (MDR), leading to a decrease in long-term anticancer therapeutic efficacy. An ideal cancer therapy requires a personalized and specialized medication delivery method capable of eradicating even the last cancer cell responsible for disease recurrence. RESULTS: Nanotechnology provides effective drug delivery mechanisms, allowing it to serve both therapeutic and diagnostic purposes. Nanotechnology-based formulations are widely used to accurately target the target organ, maintain drug load bioactivity, preferentially accumulate the drug at the target location, and reduce cytotoxicity. CONCLUSION: The key benefits of this drug delivery are that it improves pharmacological activity, solubility, and bioavailability and reduces toxicity in the target tissue by targeting ligands, allowing for new innovative treatment methods in an area that is desperately required. The goal of this review is to highlight possible research on nanotechnologybased delivery systems for cancer detection and treatment.

Graph Theoretical analysis, in silico modeling and molecular dynamic studies of (5-((2-chloropyridin-4-yl)oxy)-3-phenyl-1H-pyrazol-1-yl)-2-(4-substituted phenyl)-N,N-dimethylethen-1-amine derivatives for the treatment of breast cancer.

BACKGROUND: We synthesized a series of novel amide derivatives of (5-((2-chloropyridin-4-yl)oxy)-3-phenyl-1H-pyrazol-1-yl)-2-(4-substituted phenyl)-N,N-dimethylethen-1-amine [5a-5r] and assessed for their antiproliferative activity against human breast cancer cell line MCF7 by using MTT assay. Graph Theoretical analysis, in silico modeling, molecular dynamic studies, and ADME profile were screened for the synthesized compounds. Based on the observed report, the significant compounds were chosen for their anticancer activity. Graph Theoretical analysis, in silico modeling and molecular dynamic studies of (5-((2-chloropyridin-4-yl)oxy)-3-phenyl-1H-pyrazol-1-yl)-2-(4-substitutedphenyl)-N,N-dimethylethen-1-amine derivatives for the treatment of breast cancer. METHODS: 5-((2-chloropyridin-4-yl)oxy) (2-phenyl-1H-pyrazol-1-yl)-3-phenyl-1H-pyrazol-1-yl)-3-phenyl-1H-pyrazol-1- (4-substituted phenyl) -N,N-dimethylethen-1-amine [5a-5r] was synthesized using 2-bromo-1-phenylethanone and (5-(2-chloropyridin-4-yloxy)-3-phenyl-1H-pyrazol-1-yl)-N,N-dimethylmethanamine with different aromatic aldehydes and their characterization studies were evaluated by IR, NMR, and mass spectral analysis. RESULTS: The compound 2-(4-methylphenyl)-1-(5-((2-chloropyridin-4-yl)oxy)-3-phenyl-1H-pyrazol-1-yl)-N,N-dimethylethen-1-amine 5a and 2-(2-methylphenyl)-1-(5-((2-chloro pyridin-4-yl)oxy)-3-phenyl-1H-pyrazol-1-yl)-N,N-dimethylethen-1-amine 5c in the amide part exhibited promising cytotoxic activity against all cell lines with IC50 values of 3.3 mM for MCF-7 cells, and produced dramatic cell cycle arrest at EGFR phase as an indicator of apoptotic cell death induction. CONCLUSION: Based on their high potency in the cellular environment, these straightforward pyrazole-3-carboxamide derivatives may possess the potential to design more potent compounds for intervention with cancer cell proliferation.