Antimalarial and antiproliferative evaluation of bis-steroidal tetraoxanes.
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).
Opsenica
Dejan
D
Institute of Chemistry, Technology and Metallurgy, Belgrade, Yugoslavia.
Angelovski
Goran
G
Pocsfalvi
Gabriella
G
Juranić
Zorica
Z
Zizak
Zeljko
Z
Kyle
Dennis
D
Milhous
Wilbur K
WK
Solaja
Bogdan A
BA
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*
D000962:Antimalarials; D000970:Antineoplastic Agents; D045568:Tetraoxanes