An efficient synthesis of indolo[2,3-b]quinoline guanidine derivatives with their in vitro and in vivo study.

An optimization of the guanidylation process by verifying the efficacy of common guanylation reagents in order to obtain the guanidine derivatives of indolo[2,3-b]quinoline has been performed. As a result, a high-yield procedure using N,N'-di-Boc-N''-triflylguanidine was applied to synthesize the guanidine derivative of indolo[2,3-b]quinoline 1 in a gram scale for specific in vitro and in vivo biological research. Extensive studies on the antiproliferative activity against eight human tumor cell lines were completed. Compound 1 revealed the highest activity against A549 lung adenocarcinoma and MCF7 breast cancer cell lines. Thus, 1 was evaluated for the in vivo anticancer activity against 4T1 mammary gland carcinoma and KLN205 murine lung carcinoma in mouse models. The anticancer effect was observed in the KLN205 model with a 37% tumor growth inhibition at the 20 mg/kg dose. This anticancer activity of 1 was comparable to that of cyclophosphamide which inhibited murine lung tumor growth in the range of 27-43% at the dose of 100 mg/kg. The biochemistry research after 1 admission, including measurements of blood parameters like alanine aminotransferase, aspartate aminotransferase, lactate dehydrogenase, and urea and creatinine, were also performed.

Comprehensive review of α-carboline alkaloids: Natural products, updated synthesis, and biological activities.

α-carboline (9H-pyrido[2,3-b]indole), contains a pyridine ring fused with an indole backbone, is a promising scaffold for medicinal chemistry. In recent decades, accumulating evidence shows that α-carboline natural products and their derivatives possess diverse bioactivities. However, hitherto, there is no comprehensive review to systematically summarize this important class of alkaloids. In this perspective, this paper represents the first review to provide a comprehensive description of α-carbolines including natural products, updated literature of synthesis, and their diverse biological activities. Their biological activities including antitumor, anti-microbial, anti-Alzheimer's disease, anti-atherosclerosis, and antioxidant activities were hilighted. And the targets and the main structure activity relationships (SARs) will be presented. Finally, challenges and future directions of this class of compounds will be discussed. This review will be helpful in understanding and encouraging further exploration for this group of alkaloids.

Ultrasound-assisted Synthesis of 6-substituted indolo[2,3-b]quinolines: their Evaluation as Potential Cytotoxic Agents.

BACKGROUND: The indolo[2,3-b]quinoline framework is often found in various natural products displaying a range of pharmacological activities. This is an attractive template for the design and discovery of potential drugs especially for the identification of new anticancer agents. METHODS: The synthesis of 6-substituted indolo[2,3-b]quinolones was undertaken and carried out using a ultrasound assisted method involving two sequential C-N bond forming reactions between 3-(2- bromophenyl)-2-chloroquinoline and amines in a single pot in the presence of Pd(OAc)2 and a ligand (S)-BINAP. All the synthesized compounds were tested in vitro against two cancer cell lines e.g. MCF7 and HepG2 along with non-cancerous HEK293 cell lines. RESULTS: Two of these compounds showed promising and selective growth inhibition of MCF7 cell lines and one induced significant apoptosis in cancer (MCF7) cells. CONCLUSION: Compounds based on indolo[2,3-b]quinolone framework may be useful for the identification of new cytotoxic agents thereby potential cure for breast cancer.

Selective detection of fluoride via amplified donor-acceptor interaction of 6H-indolo[2,3-b]quinoline.

In this report, 6H-indolo[2,3-b]quinoline (hereafter 2a) was synthesized and employed as an optical chemosensor for fluoride. The sensitivity of 2a towards fluoride was established from the change in both the absorption and emission signals. The various in-situ1H NMR, UV-Vis, and density functional studies indicate that the 1:2 binding interaction between 2a and fluoride followed by deprotonation to its corresponding di-anion (2a2-), which in turn boosted the donor-acceptor interaction between indole and quinoline moiety in 2a2-via expansion of torsion angle by 10.2° as compared to 2a. Consequently the significant changes in both the absorption and emission signal of 2a allow us to detect and estimate the concentration of fluoride up to 0.2 µM from the mixture of different anions.