Design, synthesis, and antiproliferative activity of new 1H-pyrrolo[3,2-c]pyridine derivatives against melanoma cell lines

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 IC50 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.

A series of diarylureas and diarylamides possessing 1H-pyrrolo[3,2-c]pyridine scaffold was synthesized. Their in vitro antiproliferative activities against human melanoma cell lines and NIH3T3 fibroblasts were evaluated.Figure optionsDownload as PowerPoint slideHighlights
► New diarylureas and diarylamides with 1H-pyrrolo[3,2-c]pyridine scaffold were synthesized.
► Their in vitro antiproliferative activity against A375P human melanoma cell line was tested.
► IC50 values for compounds 8b, 8g, and 9a–e were in nanomolar range against A375.
► IC50 values of 8g and 9d were in nanomolar range over another 3 and 7 cell lines, respectively.
► Compounds 8b, 8g, 9b–d, and 9i showed high selectivity towards A375P cells compared with NIH3T3 fibroblasts.