Withaferin A and Withanolide D Analogues with Dual Heat-Shock-Inducing and Cytotoxic Activities: Semisynthesis and Biological Evaluation.

Withanolides constitute a valuable class of bioactive natural products because some members of the class are known to exhibit cytotoxic activity and also induce a cytoprotective heat-shock response. In order to understand the relationship between their structures and these dual bioactivities of the withanolide scaffold, we obtained 25 analogues of withaferin A (WA) and withanolide D (WD) including 17 new compounds by semisynthesis involving chemical and microbial transformations. Hitherto unknown 16ß-hydroxy analogues of WA and WD were prepared by their reaction with triphenylphosphine/iodine, providing unexpected 5ß-hydroxy-6α-iodo analogues (iodohydrins) followed by microbial biotransformation with Cunninghamella echinulata and base-catalyzed cyclization of the resulting 16ß-hydroxy iodohydrins. Evaluation of these 25 withanolide analogues for their cytotoxicity and heat-shock-inducing activity (HSA) confirmed the known structure-activity relationships for WA-type withanolides and revealed that WD analogues were less active in both assays compared to their corresponding WA analogues. The 5ß,6ß-epoxide moiety of withanolides contributed to their cytotoxicity but not HSA. Introduction of a 16ß-OAc group to 4,27-di- O-acetyl-WA enhanced cytotoxicity and decreased HSA, whereas introduction of the same group to 4- O-acetyl-WD decreased both activities.

Cytotoxic withanolides from Acnistus arborescens.

Three cytotoxic withanolides, two with new structures, were isolated from the leaves of Acnistus arborescens and their structures determined by a combination of 1D and 2D NMR, mass spectral, and molecular modeling studies. Dereplication analysis of the ethyl ether extract was useful for evaluating the components showing significant cytotoxic activity.

Assessment of Volatile Chemical Composition of the Essential Oil of Jatropha ribifolia (Pohl) Baill by HS-SPME-GC-MS Using Different Fibers.

The chemical composition of essential oil and volatile obtained from the roots of Jatropha ribifolia (Pohl) Baill was performed in this work. The Clevenger extractor was utilized in hydrodistillation of oil and chemical composition determined by gas chromatography coupled with mass spectrometry detector (GC-MS). The identification of compounds was confirmed by retention index (Kovats index) obtained from a series of straight chain alkanes (C7-C30) and by comparison with NIST and ADAMS library. A total of 61 compounds were identified in essential oil by GC-MS. The extraction of volatile was performed also by the use of the solid phase microextraction (SPME) with four different fibers. The essential oil extraction was extremely rapid (15 s) to avoid saturation of the fiber and the MS detector. The majority of the composition of essential oil is the terpenes: ß-pinene (major compound 9.16%), ß-vatirene (8.34%), α-gurjunene (6.98%), α-pinene (6.35%), camphene (4.34%), tricyclene (3.79%) and dehydro aromadendrene (3.52%) it and aldehydes and alcohols. Through the SPME it was possible to determine the nine volatile compounds not identified in oil 2,3,4-trimethyl-2-cyclopenten-1-one, α-phellandrene, 3-carene, trans-p-mentha-2,8-dienol, pinocamphone, D-verbenon, 1,3,3-trimethyl-2-(2-methyl-cyclopropyl)-cyclohexene, 2,4-diisocyanato-1-methylbenzene, and (6-hydroxymethyl-2,3-dimethylehenyl) methanol.

Isolation, structural identification and cytotoxic activity of hexanic extract, cyperenoic acid, and jatrophone terpenes from Jatropha ribifolia roots

The cytotoxicity of a hexanic fraction produced from the ethanolic crude extract, obtained from Jatropha ribifolia (Pohl) Baill, Euphorbiaceae, roots was evaluated against ten human cancer cell lines (MCF-7, NCI-ADR/RES, OVCAR-3, PC-3, HT-29, NCI-H460,786-O, UACC-62, K-562, U251) compared with doxorrubicine as positive control. Compounds jatrophone and cyperenoic acid were isolated from the hexanic extract and characterized by spectroscopic techniques (NMR of ¹H, 13C and IR). The in vitro antiproliferative activity of jatrophone showed selectivity in a concentration dependent way with Total Inhibition growth of: glioma 0.57 µg mL-1 (U251), breast cancer 9.2 µg mL-1 (MCF-7), adriamycin-resistant ovarian cancer 0.96 µg mL-1 (NCI-ADR/RES), kidney 4.2 µg mL-1 (786-0), prostate cancer 8.4 µg mL-1 (PC-3), colon cancer 16.1 µg mL-1 (HT29) and leukemia 0.21 µg mL-1 (K-562).