Structure-antitubulin activity relationships in steganacin congeners and analogs. Inhibition of tubulin polymerization in vitro by (.+-.)-isodeoxypodophyllotoxin

Abstract

A new series of 23 synthetic analogues of the naturally occurring antitumor lignan steganacin was tested for the inhibition of microtubule assembly in vitro. Interestingly, (+/-)-isopicrostegane (I50 = 5 microM) was found to be almost as active as (+/-)-steganacin(I50 = 3.5 microM). On the other hand, racemic isodeoxypodophyllotoxin has an inhibiting activity of microtubule assembly comparable to that of (-)-podophyllotoxin, whereas (-)-isodeoxypodophyllotoxin is totally inactive.

Regioselective hydrostannation of diarylalkynes directed by a labile ortho bromine atom: An easy access to stereodefined triarylolefins, hybrids of combretastatin A-4 and isocombretastatin A-4

“…Triarylolefins were tested at different concentrations and the IC 50 was calculated only for compounds inhibiting tubulin assembly by more than 50% at 9.0 Â 10 À6 M. The tubulin assembly assay was realized according to a slightly modified Guénard's protocol [56]. The tested analogues show a moderate potency (micromolar level) related to the references compounds CA-4 and isoCA-4.…”

An Overview of Syntheses of Apogalanthamine Analogues and 7‐Aza Derivatives of Steganacin and Steganone

“…[58] These compounds inhibit the assembly of tubulin into microtubules by interacting with the colchicine binding site and have been shown to possess cytotoxic activity against several cancer cell lines. [59] While not featuring a direct benzazocine skeleton, these molecules are comprised of the basic skeleton together with an additional, fused, five-membered ring system.…”

“…[59] While not featuring a direct benzazocine skeleton, these molecules are comprised of the basic skeleton together with an additional, fused, five-membered ring system. A detailed SAR study is now available [58,60] for the steganacin-type lignan lactones which exhibits some critical structural features for the potency; the dioxolane moiety is fundamental for the cytotoxic activity; Scheme 25. Synthesis of 7-aza-isopicrostegane using oxidative cyclization method.…”

Microwave-Assisted Natural Product Chemistry

“…They were isolated from Steganotaenia Araliacea by the late S.M. Kupchan and have been demonstrated to possess significant in vivo activity against P-388 leukemia in mice and in vitro activity against cells derived from human carcinoma of the nasopharynx [145][146][147][148]. In order to increase the biological potential and to solve the problems associated with stereoselection, K. Koga et al proposed the synthesis of unnatural (-)-Steganacin 7-azaanalogues [149,150].…”