In vitro optimization of non-small cell lung cancer activity with troxacitabine, L-1,3-dioxolane-cytidine, prodrugs.
l-1,3-Dioxolane-cytidine, a potent anticancer agent against leukemia, has limited efficacy against solid tumors, perhaps due to its hydrophilicity. Herein, a library of prodrugs were synthesized to optimize in vitro antitumor activity against non-small cell lung cancer. N4-Substituted fatty acid amide prodrugs of 10-16 carbon chain length demonstrated significantly improved antitumor activity over l-1,3-dioxolane-cytidine. These in vitro results suggest that the in vivo therapeutic efficacy of l-1,3-dioxolane-cytidine against solid tumors may be improved with prodrug strategies.
Radi
Marco
M
The University of Georgia College of Pharmacy, Athens, Georgia 30602, USA.
Adema
Auke D
AD
Daft
Jonathan R
JR
Cho
Jong H
JH
Hoebe
Eveline K
EK
Alexander
Lou-Ella M M
LE
Peters
Godefridus J
GJ
Chu
Chung K
CK
D000970:Antineoplastic Agents / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology; D002289:Carcinoma, Non-Small-Cell Lung / Q000188:drug therapy*; D045744:Cell Line, Tumor; D003596:Cytosine / Q000031:analogs & derivatives* / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology; D004148:Dioxolanes / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology; D004354:Drug Screening Assays, Antitumor; D006801:Humans; D008175:Lung Neoplasms / Q000188:drug therapy*; D011355:Prodrugs / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology; D013237:Stereoisomerism; D013329:Structure-Activity Relationship
D000970:Antineoplastic Agents; D004148:Dioxolanes; D011355:Prodrugs; C074908:troxacitabine; D003596:Cytosine