TY - JOUR
T1 - Design, synthesis, and antiproliferative activity of new 1H-pyrrolo[3,2-c]pyridine derivatives against melanoma cell lines
AU - El-Gamal, Mohammed I.
AU - Jung, Myung Ho
AU - Lee, Woong San
AU - Sim, Taebo
AU - Yoo, Kyung Ho
AU - Oh, Chang Hyun
N1 - Funding Information:
We would like to thank the National Cancer Institute (NCI), Bethesda, Maryland, USA, for performing the anticancer testing over nine melanoma cell lines. We are also grateful to Korea Institute of Science and Technology (KIST) for financial support.
PY - 2011/8
Y1 - 2011/8
N2 - Synthesis of a new series of diarylureas and diarylamides having 1H-pyrrolo[3,2-c]pyridine scaffold is described. Their in vitro antiproliferative activity against A375P human melanoma cell line was tested and the effect of substituents on pyrrolo[3,2-c]pyridine nucleus was investigated. The newly synthesized compounds, except three N-tolyl derivatives (8f, 9f, and 9h), generally showed superior activity against A375P to Sorafenib. Among all of these derivatives, compounds 8b, 8g, and 9a-e showed the highest potency against A375P with IC50 in nanomolar range. In addition, compounds 8d, 8e, 8h, 9g, 9i, and 9j were more potent than Sorafenib but with IC 50 in micromolar range. Compounds 8b, 8g, 9b-d, and 9i demonstrated higher selectivity towards A375P compared with NIH3T3 fibroblasts. The most potent diarylurea 8g and diarylamide 9d were further tested and showed high potency over nine melanoma cell lines at the NCI.
AB - Synthesis of a new series of diarylureas and diarylamides having 1H-pyrrolo[3,2-c]pyridine scaffold is described. Their in vitro antiproliferative activity against A375P human melanoma cell line was tested and the effect of substituents on pyrrolo[3,2-c]pyridine nucleus was investigated. The newly synthesized compounds, except three N-tolyl derivatives (8f, 9f, and 9h), generally showed superior activity against A375P to Sorafenib. Among all of these derivatives, compounds 8b, 8g, and 9a-e showed the highest potency against A375P with IC50 in nanomolar range. In addition, compounds 8d, 8e, 8h, 9g, 9i, and 9j were more potent than Sorafenib but with IC 50 in micromolar range. Compounds 8b, 8g, 9b-d, and 9i demonstrated higher selectivity towards A375P compared with NIH3T3 fibroblasts. The most potent diarylurea 8g and diarylamide 9d were further tested and showed high potency over nine melanoma cell lines at the NCI.
KW - A375P
KW - Antiproliferative activity
KW - Diarylamide
KW - Diarylurea
KW - Melanoma
KW - Pyrrolo[3,2-c]pyridine
UR - http://www.scopus.com/inward/record.url?scp=79958278972&partnerID=8YFLogxK
U2 - 10.1016/j.ejmech.2011.04.031
DO - 10.1016/j.ejmech.2011.04.031
M3 - Article
C2 - 21592628
AN - SCOPUS:79958278972
SN - 0223-5234
VL - 46
SP - 3218
EP - 3226
JO - European Journal of Medicinal Chemistry
JF - European Journal of Medicinal Chemistry
IS - 8
ER -