Synthesis and cytotoxicity evaluation of 22,23-oxygenated stigmastane derivatives

Misharin, A. Yu.; Mehtiev, Arif R.; Morozevich, G. E.; Tkachev, Yaroslav V.; Timofeev, Vladimir P.

doi:10.1016/j.bmc.2007.10.056

Cited by 24 publications

(29 citation statements)

References 36 publications

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“…In previous articles, the authors showed a relation ship between the stereochemical configuration of the atoms in the side chain of the steroid molecule and its toxicity in tumor cells [11,13]. (22R,23R) Isomers of 22,23 dihydroxycampestane and 22,23 dihydroxyer gostane derivatives hydroxylated at the C3 atom exhib ited high toxicity in MCF 7 cells, and (22S,23S) iso mers were weakly toxic and nontoxic.…”

Section: Resultsmentioning

confidence: 96%

“…Their ability to suppress growth and induce the death of cancer cells in animals is even more interesting [9,10]. It should be noted that not only BRs with the full set of functional groups are active, but also their analogues or biosynthetic precur sors, in particular, these containing the low polar groups in the cyclic moiety [11][12][13][14].…”

Section: Introductionmentioning

confidence: 98%

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Synthesis and biological activity of the probable biosynthetic precursors of 241-norbrassinolide

et al. 2012

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A number of 24-norbrassinolide biosynthetic precursors containing low polar functional groups (3beta3-OH, 3-keto-, delta2- or 2alpha,3alpha-epoxy-) in A-cycle and (22R,23R)-diol in the side chain has been prepared. Studies of these compounds as proliferation regulators in MCF-7 human breast cancer and LnCaP human prostate adenocarcinoma cells showed that most nonpolar (22R,23R)-derivatives effectively suppressed proliferation. Dependence of proliferation on concentration of studied compounds was found in human prostate carcinoma LnCaP cells (IC50 = 13-28 microM at 72 h of incubation in a medium containing 10% FBS; suppression of DNA biosynthesis). A number of compounds induced apoptosis (23-33%); arrested cell cycle in S- and G2/M-phases; and caused partial cells detachment during prolonged incubations.

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Section: Resultsmentioning

confidence: 96%

Section: Introductionmentioning

confidence: 98%

Synthesis and biological activity of the probable biosynthetic precursors of 241-norbrassinolide

et al. 2012

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“…The synthetic versatility of epoxides has established them as useful precursors to obtain a variety of polyfunctional derivatives or rearranged compounds 41, 42, 43, 44, 45, 46, 47. Cyclic α‐epoxide enones are found in a number of natural products, but asymmetric epoxidation of their precursors is notoriously difficult 48.…”

Section: Discussionmentioning

confidence: 99%

A Peroxygenase from Chaetomium globosum Catalyzes the Selective Oxygenation of Testosterone

et al. 2017

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Unspecific peroxygenases (UPO, EC 1.11.2.1) secreted by fungi open an efficient way to selectively oxyfunctionalize diverse organic substrates, including less‐activated hydrocarbons, by transferring peroxide‐borne oxygen. We investigated a cell‐free approach to incorporate epoxy and hydroxyl functionalities directly into the bulky molecule testosterone by a novel unspecific peroxygenase (UPO) that is produced by the ascomycetous fungus Chaetomium globosum in a complex medium rich in carbon and nitrogen. Purification by fast protein liquid chromatography revealed two enzyme fractions with the same molecular mass (36 kDa) and with specific activity of 4.4 to 12 U mg−1. Although the well‐known UPOs of Agrocybe aegerita (AaeUPO) and Marasmius rotula (MroUPO) failed to convert testosterone in a comparative study, the UPO of C. globosum (CglUPO) accepted testosterone as substrate and converted it with total turnover number (TTN) of up to 7000 into two oxygenated products: the 4,5‐epoxide of testosterone in β‐configuration and 16α‐hydroxytestosterone. The reaction performed on a 100 mg scale resulted in the formation of about 90 % of the epoxide and 10 % of the hydroxylation product, both of which could be isolated with purities above 96 %. Thus, CglUPO is a promising biocatalyst for the oxyfunctionalization of bulky steroids and it will be a useful tool for the synthesis of pharmaceutically relevant steroidal molecules.

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“…A series of studies was undertaken for the purpose of evaluating the effects of 22,23-dihydroxystigmastane derivatives (natural BS and analogues) [114][115][116]. The highest cytotoxicity effect against human breast carcinoma MCF-7, human ovary carcinoma CaOv, and human prostate carcinoma LnCaP cells was observed for compounds 11 and 12 (Fig.…”

Section: Anticancer Effectsmentioning

confidence: 98%

Steroid plant hormones: Effects outside plant kingdom

2015

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Synthesis and cytotoxicity evaluation of 22,23-oxygenated stigmastane derivatives

Cited by 24 publications

References 36 publications

Synthesis and biological activity of the probable biosynthetic precursors of 241-norbrassinolide

Synthesis and biological activity of the probable biosynthetic precursors of 241-norbrassinolide

A Peroxygenase from Chaetomium globosum Catalyzes the Selective Oxygenation of Testosterone

Steroid plant hormones: Effects outside plant kingdom

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