Long-chain polyamines (oligoamines) exhibit strong cytotoxicities against human prostate cancer cells.
alpha N,(omega)N-bis(ethyl) octamine SL-11160, decamine SL-11159, dodecamine SL-11226, and tetradecamine SL-11175 were chemically synthesized. We called this class of compounds 'oligoamines'. In these compounds, each -NH(2)(+) residue is separated by four CH(2) residues. trans-Unsaturation was also introduced into the center of the oligoamine chain resulting in the trans-octamine SL-11158, trans-decamine SL-11144, trans-dodecamine SL-11172 and trans-tetradecamine SL-11227. cis-Unsaturation gave the cis-octamine SL-11157 and cis-decamine SL-11150. When assayed for their growth inhibitory effect against four human prostate cancer cell lines LnCap, DU-145, DuPro, and PC-3 by a MTT assay, the ID(50) values were less than 1 microM in all four cell lines. On day 6 of treatment, 2 microM SL-11159, SL-11144 and SL-11175 killed over five logs of DuPro cells while SL-11172 killed over four logs as determined by a colony forming efficiency (CFE) assay. In addition, SL-11159, SL-11226 and SL-11227 killed four logs of PC-3 cells. PC-3 cells are generally resistant to shorter chain polyamine analogues. Such a level of cytotoxicity in any of the prostate tumor cell lines has not been observed for any other polyamine analogues tested thus far. The DU-145 cell line was too sensitive to oligoamines to perform a CFE analysis and the DuPro cell line was too sensitive to SL-11227 treatment to obtain reproducible CFE data. Interestingly, all 10 oligoamines were efficient DNA aggregators in a cell-free system and their cytotoxicities generally parallel their capacities to aggregate DNA.
Valasinas
Aldonia
A
SLIL Biomedical Corp., 535 Science Drive, Suite C, Madison, WI 53711, USA.
Reddy
Venodhar K
VK
Blokhin
Andrei V
AV
Basu
Hirak S
HS
Bhattacharya
Subhra
S
Sarkar
Aparajita
A
Marton
Laurence J
LJ
Frydman
Benjamin
B
D000970:Antineoplastic Agents / Q000138:chemical synthesis* / Q000494:pharmacology; D002455:Cell Division / Q000187:drug effects; D045744:Cell Line, Tumor / Q000187:drug effects; D002470:Cell Survival; D004247:DNA / Q000737:chemistry / Q000378:metabolism; D004305:Dose-Response Relationship, Drug; D004354:Drug Screening Assays, Antitumor; D006801:Humans; D008297:Male; D011437:Propylamines / Q000138:chemical synthesis* / Q000494:pharmacology; D011471:Prostatic Neoplasms; D013237:Stereoisomerism; D013329:Structure-Activity Relationship; D013997:Time Factors
D000970:Antineoplastic Agents; D011437:Propylamines; D004247:DNA