11H-Pyrido[3′,2′:4,5]pyrrolo[3,2-c]cinnoline and Pyrido[3′,2′:4,5]pyrrolo[1,2-c][1,2,3]benzotriazine: Two New Ring Systems with Antitumor Activity

Abstract

Derivatives of new ring systems 11H-pyrido[3',2':4,5]pyrrolo[3,2-c]cinnoline and pyrido[3',2':4,5]pyrrolo[1,2-c][1,2,3]benzotriazine have been prepared from the key intermediates 2-(1H-pyrrolo[2,3-b]pyridin-2-yl)anilines in excellent yields (94-99%) and screened by the National Cancer Institute (Bethesda, MD) on about 60 human tumor cell lines derived from nine cancer cell types. The tested compounds exhibited antiproliferative activity against all the human cell lines, showing comparable MG_MID (mean graph midpoint) values in the range of 0.74-1.15 μM. A particular efficacy was observed against the leukemia subpanel (GI50 = 0.73-0.0090 μM). Flow cytometric analysis of the cell cycle demonstrated an increase in the percentage of cells in the G2/M phase. The compounds caused apoptosis of the cells, mitochondrial depolarization, generation of reactive oxygen species, and activation of caspase-3, caspase-8, and caspase-9. Moreover, they acted as topoisomerase I inhibitors.

New Thiazole Nortopsentin Analogues Inhibit Bacterial Biofilm Formation

“…In the framework of our research on polycyclic nitrogen systems, [16,17,18,19,20,21,22,23,24,25,26,27,28,29,30,31,32,33] particularly referring to nortopsentin alkaloid analogues [34,35,36,37,38,39], herein we report the synthesis of the new series of thiazoles 1 (Table 1) and their evaluation as antibiofilm agents. In this series of nortopsentin analogues, the imidazole core of the natural product is replaced by the thiazole ring and one of the indole units is replaced by a 7-aza-indole moiety decorated with an ethanamine chain bound to the imine nitrogen.…”

Microwave assisted one-pot green synthesis of cinnoline derivatives inside natural sporopollenin microcapsules

“…Most of heterocycles exhibit biological activities and are therefore of great importance for organic synthesis. 25 Cinnoline derivatives are an important class of N-containing heteroaromatics and found intriguing interest as a privileged structures utilised as potential anticancer, 26,27 anti-inammatory, 28 antibacterial, 29 uorescent agents 30 cell imaging 31 and in designing liquid crystals. 32,33 We have used in the current study a novel polyfunctional cinnoline derivative based on the reaction of ethyl 5-cyano-4-methyl-1-aryl-6-oxo-1,6-dihydropyridazine-3carboxylate with nitroolens (Scheme 1) under controlled microwave irradiation that has been recently introduced by Sadek et al 34 These novel cinnoline derivatives are inevitably entail more exploration of their promising physico-chemical properties and potential applications.…”

New Tripentone Analogs with Antiproliferative Activity

“…Pyrrole-fused indoles and related aza-derivatives have emerged as an interesting class of anti-cancer agents endowed with potent activity against different human tumor cell lines and with different mechanisms of action [ 9 , 10 , 11 , 12 , 13 , 14 , 15 , 16 , 17 , 18 , 19 , 20 ]. In particular, 8 H -thieno[2,3- b ]pyrrolizinones, also known as “tripentones” ( Chart 1 ), have been shown to demonstrate significant cytotoxicity against tumor cells in the submicro-nanomolar range [ 21 , 22 ].…”