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Steroid sulfatase (STS) is a sulfatase enzyme that catalyzes the conversion of sulfated steroid precursors to free steroid. The inhibition of STS could abate estrogenic steroids that stimulate the proliferation and development of breast cancer, and therefore STS is a potential target for adjuvant endocrine therapy. In this study, a series of 3-benzylaminocoumarin-7-O-sulfamate derivatives targeting STS were designed and synthesized. Structure-relationship activities (SAR) analysis revealed that attachment of a benzylamino group at the 3-position of coumarin improved inhibitory activity. Compound 3j was found to have the highest inhibition activity against human placenta isolated STS (IC 50   0.13 μM) and MCF-7 cell lines (IC 50 1.35 µM). Kinetic studies found compound 3j to be an irreversible inhibitor of STS, with K I and k inact value of 86.9 nM and 158.7 min -1 , respectively., Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2020 Elsevier Inc. All rights reserved.)

Colon cancer is one of the most lethal cancers worldwide even with the significant progress made in screening techniques and therapeutic agents. Genetic mutations in tumors complicated the treatments, and the survival rate remains low for patients at late or metastatic stages. KRAS gene mutation which leads to failure of the EGFR targeted therapies stands for an example of the challenges in clinical sites. Therefore, development of novel agents for colon cancer treatment is in need. Natural and synthetic coumarin derivatives have been suggested with various biological activities with pharmacologic potential including anti-cancer capacity. Here in this study, five coumarin derivatives, include trifluoromethyl-, dimethoxy-, and/or nitro-substitutions at different positions, were synthesized. Their cancer inhibition potential was investigated in various cancer cell lines. Our data demonstrated that one nitro-coumarin derivate, 5,7-Dimethoxy-4-methyl-6-nitro-chromen-2-one, exhibits cytotoxicity specifically towards colon cancer cells under competitive EC 50 . Our results showed that this compound can effectively suppress colon cancer cells harboring either wild type or mutant KRAS genes, and that it could inhibit short-term proliferation, long term proliferation, and migration capacities of cancer cells. Finally, we demonstrated that this coumarin derivate facilitates cancer cell death through activation of apoptosis pathway. Our results suggest that this coumarin derivate is a promising lead drug worth further investigation and development for future cancer treatment., (Copyright © 2019 Elsevier B.V. All rights reserved.)

Coumarin derivatives are used as fluorescent dyes and medicines. They also have some notable physiological effects, including the acute hepatoxicity and carcinogenicity of certain aflatoxins, the anticoagulant action of dicoumarol, and the antibiotic activity of novobicin and coumerymycin A1. Because the number of drug resistant strains is increasing at present, the synthesis of new antibacterial compounds is one of the critical methods for treating infectious diseases. Therefore, a series of coumarinsubstituted derivatives, namely 4-hydroxy- and 7-hydroxycoumarins, and 3-carboxycoumarins were synthesized. 4-Hydroxycoumarin derivatives 4a-c underwent rearrangement reactions. Both 4- and 7-hydroxycoumarins were treated with activated aziridines which produced series of ring-opened products 7, 8, 10, and 11. 3-Carboxy-coumarin amide dimer derivatives 14-21 were prepared by reacting aliphatic alkylamines and alkyldiamines with PyBOP and DIEA. In this study, we use a new technique called modified micro-plate antibiotic susceptibility test method (MMAST), which is more convenient, more efficient, and more accurate than previous methods and only a small amount of the sample is required for the test. Some of the compounds were produced by reactions with acid anhydrides and demonstrated the ability to inhibit Gram-positive microorganisms. The dimer derivatives displayed lower antibacterial activities.

This study examines the synthesis and antibacterial activities of 5,7-dihydroxycoumarin derivatives, whose structures were confirmed using analytical and spectral data. Twenty compounds were tested for their antibacterial activities against five microbial species such as E. coli, S. aureus, K. pneumonia, P. aeruginosa, and S. typhimurium were studied. Compounds 5 and 12 exhibited the most potent activity against Staphylococcus aureus with a MIC value of 2.5 µg/mL for each of the compounds., (Copyright © 2011 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.)

Coumarin derivative 1, 5,7-dihydroxy-6-(3-methyl-1-butyryl)-4-phenyl-chromen- 2-one, has been reported to possess radical scavenging activity and DNA protection. We have synthesized a series of coumarins with structural modifications at positions C4, C5, C6 and C7 and evaluated them for their anti-UVC properties. Coumarin 7, 6-benzoyl-5,6-dihydroxy-4-phenyl-chromen-2-one, was found to have the most potent activity in protecting porcine γ-crystallin against UVC insults. Results of fluorescence assays indicated that compound 7 was capable of decreasing the loss of intensity while lens crystallins and DNA PUC19 were irradiated with UVC. Presence of compound 7 decreased hydroxyl radical levels determined by probe 1b and the free iron concentrations determined by Ferrozine reagent. The chelation assay showed that compound 7 was chelated to metal via 6-CO and 5-OH on the benzopyrone ring. The observed protective effects of compound 7 towards crystallins from insults of UVC and free radicals may be due to its iron-chelating activity and its peak absorption at 254 nm.

A series of coumarin derivatives were synthesized in two steps from phloroglucinol. The anti-inflammatory activities of these derivatives were evaluated by means of inhibiting NO production in LPS-induced RAW 264.7 cells. Derivatives 3, 8, 10, 11, and 13 exhibited low micromolar levels of anti-inflammatory activities, and these derivatives also protected DNA against hydroxyl radical attack. Coumarin derivative 8 was the most potent derivative among those tested herein against NO production in LPS-induced RAW 264.7 cells with an IC(50) value of 7.6 microM, and it effectively reduced the hydroxyl radical production by 50% at 100 microM in the electron spin resonance study.

[Display omitted] • Synthesis of 32 tricyclic sulfamates as STS irreversible inhibitors. • SAR studies revealed that adjacent halogen-bearing phenyl gave the best inhibition. • 19 m , 19v , and 19w , had K I of 0.02 to 0.11 nM against STS. • Cellular potency is significant correlated with covalent kinetics (k inact/ K I). Steroid sulfatase inhibitors block the local production of estrogenic steroids and are attractive agents for the treatment of estrogen-dependent cancers. Inspiration of coumarin-based inhibitors, we synthesized thirty-two 5-oxa-1,2,3,4-tetrahydro-2H-chromeno-(3,4-c)pyridin-8-yl sulfamates , focusing on the substitution derivatives on the adjacent phenyl ring and evaluated their abilities to block STS from human placenta and MCF-7 cells. SAR analysis revealed that the incorporation of chlorine at either meta and/or para position of the adjacent phenyl ring of the tricyclic skeleton enhanced STS inhibition. Di-substitutions at the adjacent phenyl ring were superior to mono and tri-substitutions. Further kinetic analysis of these compounds revealed that chloride-bearing compounds, such as 19 m , 19v , and 19w , had K I of 0.02 to 0.11 nM and k inact / K I ratios of 8.8–17.5 nM-1min-1, a parameter indicated for the efficiency of irreversible inhibition. We also used the docking model to illustrate the difference in STS inhibitory potency of compounds. Finally, the safety and anti-cancer activity of selected compounds 19 m , 19v , and 19w were also studied, showing the results of low cytotoxicity on NHDF cell line and being more potent than irosustat on ZR-75–1 cell, which was a hormone-dependent cancer cell line with high STS expression. [ABSTRACT FROM AUTHOR]