Search results for "IC50"

Balanced dual acting compounds targeting aromatase and estrogen receptor α as an emerging therapeutic opportunity to counteract estrogen responsive b…

2021

Abstract Breast Cancer (BC) is a leading cause of death in women, currently affecting 13% of female population worldwide. First-line clinical treatments against Estrogen Receptor positive (ER+) BC rely on suppressing estrogen production, by inhibiting the aromatase (AR) enzyme, or on blocking estrogen-dependent pro-oncogenic signaling, by targeting Estrogen Receptor (ER) α with selective Modulators/Degraders (SERMs/SERDs). The development of dual acting molecules targeting AR and ERα represents a tantalizing alternative strategy to fight ER + BC, reducing the incidence of adverse effects and resistance onset that limit the effectiveness of these gold-standard therapies. Here, in silico desi…

Formation of fumonisin B(1)-glucose reaction product, in vitro cytotoxicity, and lipid peroxidation on kidney cells.

2010

Fumonisin B(1) (FB(1)) content in corn products decreases during the heating process in foods containing reducing sugars, mainly because of the formation of N-(carboxymethyl)fumonisin B(1). In this study, a rapid method has been developed for the determination of both compounds in corn products using a high-speed blender, Ultra-Turrax, for solvent extraction and liquid chromatography-tandem mass spectrometry. The kinetics of FB(1) degradation and the formation of the Maillard adduct were studied in a model system constituted by corn bread spiked with FB(1) and heated at 160, 180, and 200 degrees C for 3, 6, 10, 15, and 20 min. FB(1) decreased from 0.96 to 0.3 mg/kg and N-(carboxymethyl)fumo…

Inhibition of 5-lipoxygenase activity by the natural anti-inflammatory compound aethiopinone

2001

Objetive and Design: We have investigated the mechanisms of action of aethiopinone, an anti-inflammatory compound from Salvia aethiopis L. roots.¶Material and Subjects: Human neutrophils from healthy volunteers and murine peritoneal macrophages. Swiss mice were randomly divided into groups of six animals.¶Treatment: Test compounds were applied topically in the mouse ear oedema test. In the air pouch, mice received aethiopinone (0.001-0.5 μmol/pouch or 12.5-50 mg/kg p.o.).¶Methods: LTB4 production was assayed in human neutrophils and COX-2 and iNOS activities in murine macrophages. Air pouches were induced subcutaneously in mice and injected with zymosan on the day six. Mouse ear oedema was …

MCC1019, a selective inhibitor of the Polo-box domain of Polo-like kinase 1 as novel, potent anticancer candidate

2019

Polo-like kinase (PLK1) has been identified as a potential target for cancer treatment. Although a number of small molecules have been investigated as PLK1 inhibitors, many of which showed limited selectivity. PLK1 harbors a regulatory domain, the Polo box domain (PBD), which has a key regulatory function for kinase activity and substrate recognition. We report on 3-bromomethyl-benzofuran-2-carboxylic acid ethyl ester (designated: MCC1019) as selective PLK1 inhibitor targeting PLK1 PBD. Cytotoxicity and fluorescence polarization-based screening were applied to a library of 1162 drug-like compounds to identify potential inhibitors of PLK1 PBD. The activity of compound MC1019 against the PLK1…

Cytotoxic and protein kinase inhibiting nakijiquinones and nakijiquinols from the sponge Dactylospongia metachromia.

2014

Chemical investigation of the sponge Dactylospongia metachromia afforded five new sesquiterpene aminoquinones (1-5), two new sesquiterpene benzoxazoles (6 and 7), the known analogue 18-hydroxy-5-epi-hyrtiophenol (8), and a known glycerolipid. The structures of all compounds were unambiguously elucidated by one- and two-dimensional NMR and by MS analyses, as well as by comparison with the literature. Compounds 1-5 showed potent cytotoxicity against the mouse lymphoma cell line L5178Y with IC50 values ranging from 1.1 to 3.7 μM. When tested in vitro for their inhibitory potential against 16 different protein kinases, compounds 5, 6, and 8 exhibited the strongest inhibitory activity against AL…

Antibacterial Activity and Anticancer Activity of Rosmarinus officinalis L. Essential Oil Compared to That of Its Main Components

2012

In this study, Rosmarinus officinalis L. essential oil and three of its main components 1,8-cineole (27.23%), α-pinene (19.43%) and β-pinene (6.71%) were evaluated for their in vitro antibacterial activities and toxicology properties. R. officinalis L. essential oil possessed similar antibacterial activities to α-pinene, and a little bit better than β-pinene, while 1,8-cineole possessed the lowest antibacterial activities. R. officinalis L. essential oil exhibited the strongest cytotoxicity towards three human cancer cells. Its inhibition concentration 50% (IC50) values on SK-OV-3, HO-8910 and Bel-7402 were 0.025‰, 0.076‰ and 0.13‰ (v/v), respectively. The cytotoxicity of all the test sampl…

2019

Phytochemical investigations of ethanol root bark and stem bark extracts of Cleistochlamys kirkii (Benth.) Oliv. (Annonaceae) yielded a new benzopyranyl cadinane-type sesquiterpene (cleistonol, 1) alongside 12 known compounds (2–13). The structures of the isolated compounds were established from NMR spectroscopic and mass spectrometric analyses. Structures of compounds 5 and 10 were further confirmed by single crystal X-ray crystallographic analyses, which also established their absolute stereochemical configuration. The ethanolic crude extract of C. kirkii root bark gave 72% inhibition against the chloroquine-sensitive 3D7-strain malaria parasite Plasmodium falciparum at 0.01 μg/mL. The is…

In Situ Study of the Effect of Naringin, Talinolol and Protein-Energy Undernutrition on Intestinal Absorption of Saquinavir in Rats

2011

To study the potential interactions of naringin (NAR), talinolol (TAL) and protein-energy undernutrition (PEU) in the absorption process of saquinavir (SQV), perfusion experiments were performed in the small intestine of rats at different SQV concentrations. The results obtained demonstrated that SQV intestinal absorption was described by simultaneous passive diffusion (kdif = 3.44 hr) and saturable absorption (Vma = 127.31 lM ⁄ hr; Kma =1 0.50lM) together with a capacity-limited efflux (Vms = 270.53 lM ⁄ hr; Kms =2 3.44lM). The competitive inhibition constants of NAR on the SQV input and efflux processes were (IC50)a =3 .98l Ma nd(IC50)s = 5.00 lM, respectively. NAR significantly decreased…

2017

A new isoflavone, 8-prenylmilldrone (1), and four new rotenoids, oblarotenoids A–D (2–5), along with nine known compounds (6–14), were isolated from the CH2Cl2/CH3OH (1:1) extract of the leaves of Millettia oblata ssp. teitensis by chromatographic separation. The purified compounds were identified by NMR spectroscopic and mass spectrometric analyses, whereas the absolute configurations of the rotenoids were established on the basis of chiroptical data and in some cases by single-crystal X-ray crystallography. Maximaisoflavone J (11) and oblarotenoid C (4) showed weak activity against the human breast cancer cell line MDA-MB-231 with IC50 values of 33.3 and 93.8 μM, respectively.

Discovery of new antimalarial compounds by use of molecular connectivity techniques.

1999

Abstract Molecular connectivity has been applied to the search for new compounds with antimalarial activity. Linear discriminant analysis and connectivity functions were used to select several potentially suitable drugs which were tested for antimalarial properties by use of an in-vitro micro test which estimates parasite growth by measurement of incorporation of [3H]hypoxanthine. Hexetidine stands out among the compounds selected. Activity assays were performed with Plasmodium falciparum passou and 3CD7 strains, for which the IC50 values (doses resulting in 50% inhibition) were 320 and 400 ng mL−1 respectively. These results are comparable with those obtained for quinine chlorhydrate (IC50…