Indolo[3,2-b]quinolines: Synthesis, Biological Evaluation and Structure Activity-Relationships

Abstract

The tetracyclic indolo[3,2-b]quinoline ring system constitutes an important structural moiety in natural products exhibiting numerous biological activities. In particular, indolo [3, 2-b]quinoline, commonly known as linear quindoline is of particular interest, because of its rigid structure and scope of derivatization. Although the core linear quindoline skeleton shows little or no activity in several biological systems, introduction of a methyl group on the N-5 atom leading to cryptolepine induces remarkable activity against a broad spectrum of biological targets. A number of analogs of quindoline and cryptolepine have been synthesized, incorporating various functional groups on the core quindoline skeleton leading to improved biological activities. In this review, we describe various synthetic methodologies leading to the quindoline scaffold, the biological activities and the structure activity relationships (SAR) of quindoline derivatives toward different disease states to give a better picture of the importance of this moiety in medicinal chemistry.

δ-Carbolines and their ring-opened analogs: Synthesis and evaluation against fungal and bacterial opportunistic pathogens

“…Using methods we and others previously reported, [5, 6] we were able to obtain the compounds of interest in good yields. The first step in the synthesis of the δ-carbolinium compounds, 11a-j , involved coupling commercially available substituted phenyl boronic acids or halides 5 , with 3-aminopyridine, 6 to give substituted phenylaminopyridines, 7 .…”

Efficient Synthesis of 1,9-Substituted Benzo[h][1,6]naphthyridin-2(1H)-ones and Evaluation of their Plasmodium falciparum Gametocytocidal Activities

“…Quinoline-based heterocycles have attracted much attention from both synthetic chemists and medicinal chemists due to their interesting anticancer, 1 antimalarial, 2 antibacterial, 3 antimycobacterial, 4 anti-inflammatory, 5 antihypertensive, 6 antiviral, 7 and anti-oxidant activities. 8 Several marketed drugs such as quinine and cabozantinib contain the quinoline scaffold.…”

Tandem Reductive Cyclization–Dehydration Approach for the Synthesis of Cryptolepine Hydroiodide and Its Analogues

“…Under acidic conditions, cryptolepine exists in its salt form (see Figure 1) and displays a wide range of biological activities6 such as exhibiting antibacterial, antimalarial, antifungal, antithrombotic, vasodilatory, antihyperglycemic, anticancer, cytotoxic, anti‐inflammatory, hypotensive, antipyretic, and antimuscarinic properties as well as acting as a presynaptic α‐adrenoceptor blocking agent.…”

“…Because of its broad spectrum of bioactivities and its unique structural features, cryptolepine has been a target for synthetic and medicinal chemists, and these approaches have been thoroughly reviewed by Ablordeppey and co‐workers6 in 2008 and recently by us7 in 2011. It was first synthesized by Fichter and Boehringer8 in 1906 for possible use as a dye before its isolation from a natural source.…”