Synthesis and biological activity of derivatives of the marine quinone avarone.
Nine alkyl(aryl)thio derivatives of the marine sesquiterpene quinone avarone were synthesized by nucleophilic addition of thiols or thiophenol to avarone. In most cases only one regioisomer was obtained. Their cytotoxic activities, brine shrimp lethality and antibacterial activity were evaluated, as well as those of some previously synthesized avarone derivatives. Anti-HIV activity of two derivatives was tested. Electrochemical properties were determined for all the derivatives in order to obtain more accurate information on structure-activity relationships. Most derivatives showed cytotoxic activity against tumor cell lines, with IC(50) values less than 10 microM for some of them, in particular those with electron-donating substituents. The most active compound was 4'-(methylamino)avarone, with IC(50) value of 2.4 microM to melanoma Fem-X cells, and no cytotoxicity to normal lymphocytes.
Bozić
Tatjana
T
Faculty of Science, University of Belgrade, Studentski trg 12-16, 11000 Belgrade, Serbia.
Novaković
Irena
I
Gasić
Miroslav J
MJ
Juranić
Zorica
Z
Stanojković
Tatjana
T
Tufegdzić
Srdan
S
Kljajić
Zoran
Z
Sladić
Dusan
D
D000818:Animals; D000900:Anti-Bacterial Agents / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology*; D019380:Anti-HIV Agents / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology*; D000970:Antineoplastic Agents / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology; D001156:Artemia / Q000187:drug effects / Q000382:microbiology; D045744:Cell Line, Tumor; D053138:Cyclohexenes / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology; D047088:Dysidea / Q000737:chemistry; D005260:Female; D015497:HIV-1 / Q000187:drug effects*; D006367:HeLa Cells; D006801:Humans; D020128:Inhibitory Concentration 50; D015394:Molecular Structure; D011809:Quinones / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology; D012717:Sesquiterpenes / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology; D013237:Stereoisomerism; D002583:Uterine Cervical Neoplasms / Q000188:drug therapy
D000900:Anti-Bacterial Agents; D019380:Anti-HIV Agents; D000970:Antineoplastic Agents; D053138:Cyclohexenes; D011809:Quinones; D012717:Sesquiterpenes; C046374:avarone