Synthesis of 5,6‐Dimethyl‐9‐methoxy‐1‐phenyl‐6H‐pyrido[4,3‐b]carbazole Derivatives and their Cytotoxic Activity

Abstract

Starting from 2-(6-methoxy-1-methyl-9H-carbazol-2-yl)ethylamine 7 and mixed anhydrides of 4-nitrobenzoic acid or 4-methoxybenzoic acid, the corresponding 5,6-dimethyl-9-methoxy-1-(4-substituted phenyl)-6H-pyrido[4,3-b]carbazoles 11a-b, 5,6-dimethyl-9-hydroxy-1-(4-substituted phenyl)-6H-pyrido[4,3-b]carbazoles 12a, 12c, and their quaternary salts 13a-d were obtained. The four new pyridocarbazole derivatives 12a-c and 13d satisfy the international activity criterion for synthetic compounds, namely an ID(50) value lower then 4 microg/mL in preliminary in vitro cytotoxic activity screening against the A549 cell line (non-small cell lung cancer).

Photophysical Properties of Emissive Pyrido[3,2‐c]carbazole Derivatives and Apoptosis Induction: Development towards Theranostic Agents in Response to Light Stimulus

“…It is well- [a] M. Sakuma known that the natural products containing carbazole and pyridocarbazole frameworks possess high cytotoxicity.T hus, pyridocarbazoles constitute an important class of therapeutic agents in medicinal chemistry.For example;olivacine and ellipticine are natural pyridocarbazole alkaloids, which have also been shown to have anticancer activity. [24][25][26][27] Hence, in the past few years, carbazole based-compounds, such as pyridocarbazole and pyrimidocarbazole derivatives have been widely studied as promising chemotherapeutic agents. Especially,1 -substituted-6H-pyrido [4,3-b]c arbazole derivatives, synthesized by B. Tylinska and co-workers, [28] exhibit over 20 times better activity against murinel eukemia L1210 tumor cell line than ellipticine.…”

“…Thus, pyridocarbazoles constitute an important class of therapeutic agents in medicinal chemistry. For example; olivacine and ellipticine are natural pyridocarbazole alkaloids, which have also been shown to have anticancer activity . Hence, in the past few years, carbazole based‐compounds, such as pyridocarbazole and pyrimidocarbazole derivatives have been widely studied as promising chemotherapeutic agents.…”

Synthesis and Anticancer Activity of New 1‐Substituted‐6H‐pyrido[4,3‐b]carbazole Derivatives

“…One of the newly obtained compounds, namely 5,6-dimethyl-9-hydroxy-1-(4-nitrophenyl)-6H-pyrido [4,3-b]carbazole has shown significant antitumor activity on human lung cancer (A549) (IC 50 = 2.37 lM) [21]. This fact prompted us to synthesize new 1-phenyl-29-methoxy-6H-pyrido [4,3-b]carbazole derivatives 3, which were subjected for testing their cytostatic activity in vitro on human lung cancer (A549) and human kidney cancer (A498) cell lines.…”