Aim and Objective: Carbazoles and pyrrolidines derivatives exhibit a broad spectrum of biological
and pharmacological properties, which exist in numerous drugs. Due to the high significance of these two
classes of moieties in drug discovery, the synthesis of the compounds containing both of these two moieties are
Method: A metal- and catalyst-free three-component decarboxylative coupling reaction of proline, aldehyde
and 4-hydroxycarbazole has been developed. The synthesized compounds were examined for their antiproliferative
and antioxidant activities. Molecular docking studies were performed on all synthesized compounds
against tubulin structure using Schrodinger’s Glide software.
Results: This atom economic approach provides an access to pyrrolidinyl-carbazole derivatives in good yields.
The antiproliferative activity of newly synthesized compounds was investigated on both normal cell line
(CHO) and cancer cancer cell lines (MCF7, MDA-MB-231 and A549). The results indicated that, these compounds
showed selective cytotoxicity against both normal and cancer cells. In addition, most of the compounds
showed very good antioxidant activity. Molecular docking studies demonstrated that all the lead compounds
selectively occupy the colchicine binding site of the tubulin polymer.
Conclusion: In conclusion, we have developed a simple, metal- and catalyst-free three-component protocol to
access synthetically as well as biologically important pyrrolidinyl-carbazole derivatives via decarboxylative
coupling reaction involving proline, aldehydes and 4-hydroxycarbazole. The synthesized compounds were examined
for their antiproliferative and antioxidant activities. The trend in the observed antiproliferative activity
was further rationalized by molecular docking studies.