Anti-tumor 12-deoxyphorbol esters from Euphorbia cornigera.
Nine (1-8 and 10) new and two (9 and 11) known compounds have been isolated from roots of Euphorbia cornigera Boiss. Their structure and relative stereochemistry were acquired through NMR ((1)H, (13)C, COSY-45, HOHAHA, HMQC, HMBC, NOE and HMBC) spectroscopic measurements. Compounds 1-10 were identified as diesters of 13,20-O-diacyl and 11 as 13-O-acetyl of 12-deoxyphorbol. Cytotoxic activity of the compounds was investigated on human KB cells by reduction of MTT. Compounds 8-10 displayed IC(50) of 0.8, 0.5, and 1.0 microg mL(-1), respectively, whereas the activity of rest of the compounds (1-7) was either very low or (11) zero even up to 1000 microg mL(-1). The inhibition of DNA synthesis through Trypan blue exclusion and Brd-U assay was investigation to figure out the role of compounds 8-10 and concluded that these were responsible for the death of KB cells. Significant correlation has been found between the cytotoxicity and DNA cross-link and DNA strand-break formation.
Baloch
Imam Bakhsh
IB
Department of Chemistry, Gomal University, Dera Ismail Khan, Pakistan.
Baloch
Musa Kaleem
MK
Saqib
Qazi Najam us
QN
D000818:Animals; D000972:Antineoplastic Agents, Phytogenic / Q000737:chemistry / Q000302:isolation & purification / Q000494:pharmacology*; D045744:Cell Line, Tumor; D004354:Drug Screening Assays, Antitumor; D028481:Euphorbia / Q000737:chemistry*; D006801:Humans; D007509:Irritants / Q000737:chemistry / Q000302:isolation & purification / Q000494:pharmacology; D051379:Mice; D010703:Phorbol Esters / Q000737:chemistry / Q000302:isolation & purification / Q000494:pharmacology*; D013057:Spectrum Analysis / Q000379:methods
D000972:Antineoplastic Agents, Phytogenic; D007509:Irritants; D010703:Phorbol Esters