TY - JOUR
T1 - Enhancing macrocyclic diterpenes as multidrug-resistance reversers
T2 - Structure-activity studies on jolkinol D derivatives
AU - Reis, Mariana
AU - Ferreira, Ricardo J.
AU - Santos, Maria M.M.
AU - Dos Santos, Daniel J.V.A.
AU - Molnár, Joseph
AU - Ferreira, Maria José U.
PY - 2013/2/14
Y1 - 2013/2/14
N2 - The phytochemical study of Euphorbia piscatoria yielded jolkinol D (1) in a large amount, whose derivatization gave rise to 12 ester derivatives (2-13) and hydrolysis to compound 14. The in vitro modulation of P-gp of compounds 1-14 was evaluated through a combination of transport and chemosensitivity assays, using the L5178 mouse T lymphoma cell line transfected with the human MDR1 gene. Apart from jolkinol D, all derivatives (2-14) showed potential as MDR reversal agents. In this small library of novel bioactive macrocyclic lathyrane diterpene derivatives, designed to evaluate structure-activity relationships essential in overcoming multidrug resistance (MDR), some correlations between MDR reversal and molecular weight, accessible solvent areas, and octanol/water partition coefficient were identified that can contribute to the development of new selective P-gp reversal agents.
AB - The phytochemical study of Euphorbia piscatoria yielded jolkinol D (1) in a large amount, whose derivatization gave rise to 12 ester derivatives (2-13) and hydrolysis to compound 14. The in vitro modulation of P-gp of compounds 1-14 was evaluated through a combination of transport and chemosensitivity assays, using the L5178 mouse T lymphoma cell line transfected with the human MDR1 gene. Apart from jolkinol D, all derivatives (2-14) showed potential as MDR reversal agents. In this small library of novel bioactive macrocyclic lathyrane diterpene derivatives, designed to evaluate structure-activity relationships essential in overcoming multidrug resistance (MDR), some correlations between MDR reversal and molecular weight, accessible solvent areas, and octanol/water partition coefficient were identified that can contribute to the development of new selective P-gp reversal agents.
UR - http://www.scopus.com/inward/record.url?scp=84873898843&partnerID=8YFLogxK
U2 - 10.1021/jm301441w
DO - 10.1021/jm301441w
M3 - Article
C2 - 23336337
AN - SCOPUS:84873898843
SN - 0022-2623
VL - 56
SP - 748
EP - 760
JO - Journal of Medicinal Chemistry
JF - Journal of Medicinal Chemistry
IS - 3
ER -