213920-24-2

Upstream product

• 2555-37-5 3-acetyl-4-hydroxychromen-2-one 
• 459-57-4 4-fluorobenzaldehyde 
• 1076-38-6 4-hydroxy[1]benzopyran-2-one 

Downstream Products

• 1417540-54-5 C₂₄H₁₆FNO₃S 

Relevant academic research and scientific papers

Angiokinase inhibition of VEGFR-2, PDGFR and FGFR and cell growth inhibition in lung cancer: Design, synthesis, biological evaluation and molecular docking of novel azaheterocyclic coumarin derivatives

The present work represents the design and synthesis of some azaheterocyclic coumarin derivatives which are evaluated as anti-lung cancer agents. Ten out of the twenty azaheterocyclic compounds showed superior activity than the standard drug staurosporine against non-small cell lung cancer (A549). Representing the four different azaheterocyclic series, compounds 4a, 5d, 6e, and 7d, which demonstrated IC50s of 2.38, 2.39, 1.05 and 3.98 μM, respectively, each exhibiting the best cytotoxicity in its group, were selected for further assessment of their toxicity on normal lung cells (WI-38). Compound 4a was selected for further investigations because it remarkably revealed less cytotoxicity (IC50 = 53.76 μM) than 7d (IC50 = 19.95 μM) on (WI-38) compared to staurosporine (IC50 = 24.41 μM). 4a was assessed for its ability to inhibit the angiokinases VEGFR-2, PDGFR, FGFR and the growth factor EGFR, remarkably it showed better VEGFR-2, PDGFR, FGFR inhibition than the reference drugs used and exhibited as well noticeable EGFR inhibition. Going further, 4a was capable of arresting the cell cycle at pre-G1 phase and S phase and inducing apoptosis. Moreover, the capability of the target 4a to interact with the key amino acids of VEGFR-2 binding site was detected by molecular docking. Finally, the in silico physicochemical properties of 4a were studied.

New Coumarin Derivatives as Anti-Breast and Anti-Cervical Cancer Agents Targeting VEGFR-2 and p38α MAPK

Breast and cervical cancers are the most common gender-specific cancers affecting women worldwide. In this investigation, we highlighted the synthesis, VEGFR-2 and p38α MAPK inhibitory activity of new series of fluorinated coumarin-based derivatives featuring a variety of bioactive chemical moieties attached or fused to the coumarin nucleus at the 3 and/or 4 position. The bioactive inhibitors were further assessed for their anti-proliferative effect against human MCF-7 breast cancer and HeLa cervical cancer cell lines, respectively. Most of the tested compounds showed potent preferential inhibition effects against human VEGFR-2 and remarkable anticancer activities in the human breast cancer cell line MCF-7. Compounds 29, 24, and 2 displayed the highest inhibitory activity against VEGFR-2 (94% inhibition) and they were the most potent anticancer agents toward MCF-7 cancer cells with IC50 values of 7.90, 8.28, and 8.30 μg/mL, respectively. Compound 13 inhibited p38α MAPK phosphorylation with a significant reduction in % cell viability against HeLa cancer cells at 10 and 30 μM. Docking experiments carried out on VEGFR-2 and p38 MAPK crystallographic structures revealed that the active compounds bind to the active sites through H-bonds, arene–cation, and hydrophobic π–π interactions. QSAR analysis demonstrated considerable correlation coefficient (R2 = 0.76969) and root mean square error (RMSE = 0.10446) values. Also, the residual values between the experimental pIC50 and predicted pIC50 are very close, indicating the reliability of the established QSAR model.

Antileishmanial activity of novel indolyl-coumarin hybrids: Design, synthesis, biological evaluation, molecular docking study and in silico ADME prediction

In present work we have designed and synthesized total twelve novel 3-(3-(1H-indol-3-yl)-3-phenylpropanoyl)-4-hydroxy-2H-chromen-2-one derivatives 13(a-l) using Ho3+doped CoFe2O4nanoparticles as catalyst and evaluated for their potential antileishmanial and antioxidant activities. The compounds 13a, 13d and 13h were found to possess significant antileishmanial activity (IC50value = 95.50, 95.00 and 99.00 μg/mL, respectively) when compared to the standard sodium stibogluconate (IC50= 490.00 μg/mL). The compounds 13a (IC50= 12.40 μg/mL), 13d (IC50= 13.49 μg/mL), 13g (IC50= 13.24 μg/mL) and 13l (IC50= 13.74 μg/mL) had shown good antioxidant activity when compared with standards butylated hydroxy toluene (IC50= 16.5 μg/mL) and ascorbic acid (IC50= 12.8 μg/mL). After performing molecular docking studies, it was found that compounds 13a and 13d had potential to inhibit pteridine reductase 1 enzyme. In silico ADME pharmacokinetic parameters had shown promising results and none of the synthesized compounds had violated Lipinski's rule of five. Thus, suggesting that compounds from the present series can serve as important gateway for the design and development of new antileishmanial as well as antioxidant agent.

Evaluation of Structurally Diverse Benzoazepines Clubbed with Coumarins as Mycobacterium tuberculosis Agents

Tuberculosis caused by Mycobacterium tuberculosis remains a leading cause of mortality worldwide into 21st century. In continuation with our anti-tuberculosis research programme, in this work, we have prepared molecularly diverse coumarins clubbed with benzothiazepines as well as its aza-analogues-benzodiazepines by molecular hybridization. The resulting compounds were screened for their M. tuberculosis activity against H37Rv strains using microplate alamar blue assay. Among the designed diversity, the compounds 5k, 5n and 5o were found significantly active in primary anti-tuberculosis assay at minimum inhibitory concentration 50 values of 5k and 5o in level-2 screening were observed as >10μg/mL and 3.63μg/mL, respectively. Design and synthesis of more focused library and its three-dimensional quantitative structure activity relationship analysis are underway. In the present work, various coumarins clubbed with benzo(thi)diazepines were evaluated for their M. tuberculosis activity against H37Rv strains using MABA assay. The IC50 values of two analogs (compounds 5k and 5o) in level-2 screening were observed as >10μg/mL and 3.63μg/mL respectively.