97355-91-4

Upstream product

• 10031-82-0 4-ethoxybenzaldehyde 
• 99-93-4 4-Hydroxyacetophenone 

Downstream Products

• 1186317-37-2 C₁₉H₂₀O₄ 
• 1186317-58-7 C₂₁H₂₂O₅ 

Relevant academic research and scientific papers

Novel chalcone and flavone derivatives as selective and dual inhibitors of the transport proteins ABCB1 and ABCG2

During cancer chemotherapy, certain cancers may become cross-resistant to structurally diverse antineoplastic agents. This so-called multidrug resistance (MDR) is highly associated with the overexpression of ATP-binding cassette (ABC) transport proteins. These membrane-bound efflux pumps export a broad range of structurally diverse endo- and xenobiotics, including chemically unrelated anticancer agents. This translocation of drugs from the inside to the outside of cancer cells is mediated at the expense of ATP. In the last 40 years, three ABC transporters – ABCB1 (P-gp), ABCC1 (MRP1), and ABCG2 (BCRP) – have mainly been attributed to the occurrence of MDR in cancer cells. One of the strategies to overcome MDR is to inhibit the efflux transporter function by small-molecule inhibitors. In this work, we investigated new chalcone- and flavone-based compounds for selective as well as broad-spectrum inhibition of the stated transport proteins. These include substituted chalcones with variations at rings A and B, and flavones with acetamido linker at position 3. The synthesized molecules were evaluated for their inhibitory potential against ABCB1, ABCC1, and ABCG2 in calcein AM and pheophorbide A assays. In further investigations with the most promising candidates from each class, we proved that ABCB1- and ABCG2-mediated MDR could be reversed by the compounds. Moreover, their intrinsic toxicity was found to be negligible in most cases. Altogether, our findings contribute to the understanding of ABC transport proteins and reveal new compounds for ongoing evaluation in the field of ABC transporter-mediated MDR.

Study on the interaction of 4'-hydroxychalcones and their mannich derivatives with calf thymus dna by tlc and spectroscopic methods, a dna cleavage study

Background: Phenolic Mannich bases derived from hydroxychalcones show remarkable cytotoxic potencies towards cancer cell lines. However, the exact mechanism of action is still partially uncleared. Objective: Interaction of two hydroxychalcones and their M

Discovery of novel human inosine 5′-monophosphate dehydrogenase 2 (hIMPDH2) inhibitors as potential anticancer agents

The enzyme inosine 5′-monophosphate dehydrogenase (IMPDH) catalyzes an essential step in the de novo biosynthesis of guanine nucleotides, and thus regulates the guanine nucleotide pool required for cell proliferation. Of the two isoforms, human IMPDH type 2 (hIMPDH2) is a validated molecular target for potential immunosuppressive, antiviral and anticancer chemotherapy. In search of newer hIMPDH2 inhibitors as potential anticancer agents, three novel series (A: 5-aminoisobenzofuran-1(3H)-one, B: 3,4-dimethoxyaniline and C: benzo[d]-[1,3]dioxol-5-ylmethanamine) were synthesized and evaluated for in vitro and cell-based activities. A total of 37 molecules (29–65) were screened for their in vitro hIMPDH2 inhibition, with particular emphasis on establishing their structure–activity relationship (SAR) trends. Eight compounds (hits, 30, 31, 33–35, 37, 41 and 43) demonstrated significant enzyme inhibition (>70% @ 10 μM); especially the A series molecules were more potent than B series (50 values for the hits ranged from 0.36 to 7.38 μM. The hits displaying >80% hIMPDH2 inhibition (30, 33, 35, 41 and 43) were further assessed for their cytotoxic activity against cancer cell lines such as MDA-MB-231 (breast adenocarcinoma), DU145 (prostate carcinoma), U87 MG (glioblastoma astrocytoma) and a normal cell line, NIH-3T3 (mouse embryonic fibroblast) using MTT assay. Most of the compounds exhibited higher cellular potency against cancer cell lines and notably lower toxicity towards NIH-3T3 cells compared to mycophenolic acid (MPA), a prototypical hIMPDH2 inhibitor. Two of the series A hits (30 and 35) were evaluated in human peripheral blood mononuclear cells (hPBMC) assay and found to be better tolerated than MPA. The calculated/predicted molecular and physicochemical properties were satisfactory with reference to drug-likeness. The molecular docking studies clearly demonstrated crucial interactions of the hits with the cofactor-binding site of hIMPDH2, further providing critical information for refining the design strategy. The present study reports the design and discovery of structurally novel hIMPDH2 inhibitors as potential anticancer agents and provides a guide for further research on the development of safe and effective anticancer agents, especially against glioblastoma.

Synthesis of a series of novel dihydroartemisinin derivatives containing a substituted chalcone with greater cytotoxic effects in leukemia cells

Fifteen dihydroartemisinin derivatives containing a substituted chalcone linked by either ether or ester were synthesized and investigated for their cytotoxicity in human leukemia HL-60 and mouse lymphoma P388 cells. These derivatives have greater antiproliferative and cytotoxic effects in both cell lines than dihydroartemisinin. Dihydroartemisinin chalcones linked by ether are more cytotoxic than dihydroartemisinin chalcones linked by ester with apoptosis induction abilities.

Synthesis and fungicidal evaluation of novel chalcone-based strobilurin analogues

Strobilurin derivatives have become one of the most important classes of agricultural fungicide due to a novel action mode, wide fungicidal spectrum, lower toxicity toward mammalian cells, and environmentally benign characteristics. To discover new strobilurin analogues with high activity against resistant pathogens, a series of new chalcone-based strobilurin derivatives are designed and synthesized by integrating a chalcone scaffold with a strobilurin pharmacophore. The preliminary bioassay showed that some of the chalcone analogues exhibited good in vivo fungicidal activities against Pseudoperoniospora cubensis and Sphaerotheca fuliginea at the dosage of 200 μg mL-1. Two compounds, (￡)-methyl 2-[2-({3-[(￡)-3-(2- chlorophenyl)acryloyl]phenoxy}methyl)phenyl]-3-meth-oxyacrylate (1e) and (E)-methyl 2-[2-({3-[(E)-3-(3-bromophenyl)acryloyl]phenoxy}methyl)phenyl]-3- methoxyacrylate (11), were found to display higher fungicidal activities against P. cubensis (EC90 = 118.52 μg ml-1 for 1e and EC 90 = 113.64 μg mL-1 for 11) than Kresoxim-methyl (EC90 = 154.92 μg mL-1) and were identified as the most promising candidates for further study. The present work demonstrated that strobilurin analogues containing chalcone as a side chain could be used as a lead structure for further developing novel fungicides. To our knowledge, this is the first report about the syntheses and fungicidal activities of chalcone-based strobilurin derivatives.