Bichromonol, a dimeric coumarin with anti-HIV activity from the stem bark of Hypericum roeperianum

Infectious diseases caused by viruses like HIV and SARS-COV-2 (COVID-19) pose serious public health threats. In search for new antiviral small molecules from chemically underexplored Hypericum species, a previously undescribed atropisomeric C8-C8’ linked dimeric coumarin named bichromonol (1) was isolated from the stem bark of Hypericum roeperianum. The structure was elucidated by MS data and NMR spectroscopy. The absolute configuration at the biaryl axis was determined by comparing the experimental ECD spectrum with those calculated for the respective atropisomers. Bichromonol was tested in cell-based assays for cytotoxicity against MT-4 (CC50 = 54 µM) cells and anti-HIV activity in infected MT-4 cells. It exhibits significant activity at EC50 = 6.6–12.0 µM against HIV-1 wild type and its clinically relevant mutant strains. Especially, against the resistant variants A17 and EFVR, bichromonol is more effective than the commercial drug nevirapine and might thus have potential to serve as a new anti-HIV lead

In vitro cytotoxicity of compounds isolated from Desbordesia glaucescens against human carcinoma cell lines

WOS:000405251800006Malignancies constitute a global health concern and chemotherapy remains the main mode of treatment. The present study was designed to evaluate the cytotoxicity of 8 compounds from Desbordesia glaucescens namely lanosta-7,24-dien-3-one (1), friedelanone (2), friedelanol (3), 3,3'-di-O-methylellagic acid (4), 3,3',4'-tri-0-methylellagic acid (5), ellagic acid (6), 3',4'-di-0-methylellagic acid 4-0-beta-o-glucopyranoside (7) and 3,3'-di-0-methylellagic acid 4'-0-beta-c-xylopyranoside (8) against 4 human carcinoma cell lines and normal CRL2120 fibroblasts. The neutral red uptake (NRU) assay was used for cytotoxicity testing. Caspase-Glo assay, cell cycle analysis, measurements of mitochondrial membrane potential (MMP) and levels of reactive oxygen species (ROS) were used to evaluate apoptosis induction. Compounds 4 and 6 as well as doxorubicin had IC50 values below 45 pM in the four tested cancer cell lines meanwhile other compounds displayed selective activity. The IC50 values ranged from 11.23 mu M (towards breast adenocarcinoma MCF-7 cells) to 44.65 mu M (colon carcinoma Caco-2 cells) for 4, from 14.07 mu M (towards MCF-7 cells) to 77.73 mu M (Caco-2 cells) for 6 and from 0.07 mu M (towards SPC212 cells) to 1.01 mu M (A549 cells) for doxorubicin. Compound 4 induced apoptosis in MCF-7 cells mediated by MMP loss. The constituents of Desbordesia glaucescens and especially ellagic acid (6) and its derivative 4 are potential cytotoxic compounds that deserve more investigations towards developing novel antiproliferative drugs against human carcinoma. (C) 2017 SAAB. Published by Elsevier B.V. All rights reserved.Scientific and Technological Research Counsel of Turkey (TUBITAK); Scientific Research Projects Commission of Anadolu University, Eskisehir, Turkey [1507F563, 1306F110]; International Science Programme, Uppsala University, Sweden (ISP) [KEN-02]V.K. and H.S. are thankful to Scientific and Technological Research Counsel of Turkey (TUBITAK) for 6 months travel grant (to V.K.) and to Scientific Research Projects Commission of Anadolu University, Eskisehir, Turkey for the funding grant 1507F563 (to V.K. and H.S.). A grant for part of this work was also provided by International Science Programme, Uppsala University, Sweden (ISP)-KEN-02 project. IC would like to thank the Scientific Research Projects Commission of Anadolu University, Eskisehir, Turkey for the funding grant (1306F110). Authors are also thankful to Sennur Gorgulti for FACS measurements