title: Antimalarial and antiproliferative evaluation of bis-steroidal tetraoxanes.
abstract: Several cis and trans bis-steroidal 1,2,4,5-tetraoxanes possessing amide terminus were synthesised and evaluated as antimalarials and antiproliferatives. The compounds exhibited submicromolar antimalarial activity against Plasmodium falciparum D6 and W2 strains. The existence of HN-C(O) moiety was found necessary for pronounced antimalarial and antiproliferative activity. In antiproliferative screen, the trans tetraoxane 6 was found to exhibit a pronounced cytotoxicity on 14 cancer cell lines. In addition, tetraoxanes 11 and 12 exhibited significant cytotoxic activity too; microscopic examination of treated HeLa cells showed morphological appearance reminiscent for apoptosis (condensed and/or fragmented nuclei).
authors.affiliation: Institute of Chemistry, Technology and Metallurgy, Belgrade, Yugoslavia.
authors.forename: Dejan
authors.initials: D
authors.lastname: Opsenica
authors.forename: Goran
authors.initials: G
authors.lastname: Angelovski
authors.forename: Gabriella
authors.initials: G
authors.lastname: Pocsfalvi
authors.forename: Zorica
authors.initials: Z
authors.lastname: Juranić
authors.forename: Zeljko
authors.initials: Z
authors.lastname: Zizak
authors.forename: Dennis
authors.initials: D
authors.lastname: Kyle
authors.forename: Wilbur K
authors.initials: WK
authors.lastname: Milhous
authors.forename: Bogdan A
authors.initials: BA
authors.lastname: Solaja
mesh_terms: D000818:Animals; D000962:Antimalarials / Q000138:chemical synthesis* / Q000494:pharmacology; D000970:Antineoplastic Agents / Q000138:chemical synthesis* / Q000494:pharmacology; D017209:Apoptosis / Q000187:drug effects; D002455:Cell Division / Q000187:drug effects; D045744:Cell Line, Tumor; D018922:HL-60 Cells; D006801:Humans; D020128:Inhibitory Concentration 50; D010963:Plasmodium falciparum / Q000187:drug effects; D013237:Stereoisomerism; D013329:Structure-Activity Relationship; D045568:Tetraoxanes / Q000138:chemical synthesis / Q000494:pharmacology*
chemical_list: D000962:Antimalarials; D000970:Antineoplastic Agents; D045568:Tetraoxanes