TY - JOUR
T1 - Design, synthesis, and antiproliferative activity of new 1H-pyrrolo[3,2-c]pyridine derivatives against melanoma cell lines. Part 2
AU - Jung, Myung Ho
AU - El-Gamal, Mohammed I.
AU - Abdel-Maksoud, Mohammed S.
AU - Sim, Taebo
AU - Yoo, Kyung Ho
AU - Oh, Chang Hyun
N1 - Funding Information:
This work was supported by Korea Institute of Science and Technology (KIST), KIST Project ( 2E22360 ). We would like to thank the National Cancer Institute (NCI), Bethesda, Maryland, USA, for performing the anticancer testing over nine melanoma cell line panel.
PY - 2012/7/1
Y1 - 2012/7/1
N2 - A new series of diarylureas and diarylamides possessing 1H-pyrrolo[3,2-c]pyridine scaffold was designed and synthesized. Their in vitro antiproliferative activities against A375P human melanoma cell line and NCI-9 human melanoma cell line panel were tested. All the target compounds, except three amino derivatives 8g, h and 9h, demonstrated superior potencies against A375P to Sorafenib. In addition, compounds 8a and 9b-f demonstrated higher potencies than Vemurafenib against A375P. Compounds 8c and 9b were 7.50 and 454.90 times, respectively, more selective towards A375P melanoma cells over NIH3T3 fibroblasts. Furthermore, compounds 8d, e and 9a-d, f demonstrated very high potencies against the nine tested melanoma cell lines at the NCI. The bisamide derivatives 9a-c, f showed 2-digit nanomolar IC 50 values over different cell lines of the NCI-9 melanoma cell lines.
AB - A new series of diarylureas and diarylamides possessing 1H-pyrrolo[3,2-c]pyridine scaffold was designed and synthesized. Their in vitro antiproliferative activities against A375P human melanoma cell line and NCI-9 human melanoma cell line panel were tested. All the target compounds, except three amino derivatives 8g, h and 9h, demonstrated superior potencies against A375P to Sorafenib. In addition, compounds 8a and 9b-f demonstrated higher potencies than Vemurafenib against A375P. Compounds 8c and 9b were 7.50 and 454.90 times, respectively, more selective towards A375P melanoma cells over NIH3T3 fibroblasts. Furthermore, compounds 8d, e and 9a-d, f demonstrated very high potencies against the nine tested melanoma cell lines at the NCI. The bisamide derivatives 9a-c, f showed 2-digit nanomolar IC 50 values over different cell lines of the NCI-9 melanoma cell lines.
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=84862170286&partnerID=8YFLogxK
U2 - 10.1016/j.bmcl.2012.05.004
DO - 10.1016/j.bmcl.2012.05.004
M3 - Article
C2 - 22647720
AN - SCOPUS:84862170286
SN - 0960-894X
VL - 22
SP - 4362
EP - 4367
JO - Bioorganic and Medicinal Chemistry Letters
JF - Bioorganic and Medicinal Chemistry Letters
IS - 13
ER -