Tetracyclic Pyrido Research Articles

In silico Design, Synthesis and Biological Evaluation of Novel Thieno[3,2-d]pyrimidine Derivatives for Cancer Therapy - A Preliminary Study on the Inhibitory Potential towards ATR Kinase Domain and PIKK Family.

Continuing our studies in the field of new heterocyclic compounds with biological interest, herein we report the synthesis and anticancer activity of new N- and S-substituted derivatives of tetracyclic pyrido[3',2' : 4,5]thieno[3,2-d]pyrimidines. In this regard, starting from the thieno[2,3-b]pyridine-2-carboxylates, the corresponding 8(9)-aminopyrido[3',2' : 4,5]thieno[3,2-d]pyrimidin-7(8)-ones, as well as chloro derivatives were obtained. Based on the latter, amino, hydrazino and S-alkyl derivatives of pyrido[3',2' : 4,5]thieno[3,2-d]pyrimidines were synthesized subsequently. The current study focuses on identifying the potential of thieno[3,2-d]pyrimidine derivatives primarily towards ATR kinase inhibition, through computational predictions, followed by synthesis and cancer cell viability studies, along with an aim to develop the core as PIKK inhibitors for cancer therapy.

Synthesis and Activity against Mycobacterium tuberculosis of Olivacine and Oxygenated Derivatives.

The tetracyclic pyrido[4,3-b]carbazole olivacine and four of its oxygenated derivatives have been synthesized by a late-stage palladium-catalyzed Heck-type cyclization of the pyrrole ring as a key step. In a test for the inhibition of the growth of Mycobacterium tuberculosis, 9-methoxyolivacine showed the most significant inhibitory activity against Mycobacterium tuberculosis, with an MIC90 value of 1.5 μM.

One-pot synthesis of highly emissive dipyridinium dihydrohelicenes.

Condensation of a pyridyl-2-carbaldehyde derivative with 2-(bromoethyl)amine hydrobromide gave tetracyclic pyrido[1,2-a]pyrido[1',2':3,4]imidazo-[2,1-c]-6,7-dihydropyrazinium dications in excellent yields. Crystal structures and NOE data demonstrated the helical character of the dications, the dihedral angles between the two pyrido groups ranging from 28-45°. An intermediate in the synthesis was also characterized. A much brighter emission compared to literature helicenes has been found, with quantum yields as high as 60 % in the range of λ=460-600 nm. Preliminary cytotoxicity studies against HT-29 cancer cells demonstrated moderate-to-good activity, with IC50 values 12-30× that of cisplatin.

ChemInform Abstract: Synthesis of a Novel Tetracyclic Pyrido[3′,2′:4,5]thieno[3,2‐b]indole System.

ChemInformVolume 44, Issue 44 Heterocyclic Compounds ChemInform Abstract: Synthesis of a Novel Tetracyclic Pyrido[3′,2′:4,5]thieno[3,2-b]indole System. E. A. Kanishcheva, E. A. Kanishcheva Kuban State Technol. Univ., Krasnodar 350072, RussiaSearch for more papers by this authorV. K. Vasilin, V. K. Vasilin Kuban State Technol. Univ., Krasnodar 350072, RussiaSearch for more papers by this authorD. R. Kasimova, D. R. Kasimova Kuban State Technol. Univ., Krasnodar 350072, RussiaSearch for more papers by this authorT. A. Stroganova, T. A. Stroganova Kuban State Technol. Univ., Krasnodar 350072, RussiaSearch for more papers by this authorG. D. Krapivin, G. D. Krapivin Kuban State Technol. Univ., Krasnodar 350072, RussiaSearch for more papers by this author E. A. Kanishcheva, E. A. Kanishcheva Kuban State Technol. Univ., Krasnodar 350072, RussiaSearch for more papers by this authorV. K. Vasilin, V. K. Vasilin Kuban State Technol. Univ., Krasnodar 350072, RussiaSearch for more papers by this authorD. R. Kasimova, D. R. Kasimova Kuban State Technol. Univ., Krasnodar 350072, RussiaSearch for more papers by this authorT. A. Stroganova, T. A. Stroganova Kuban State Technol. Univ., Krasnodar 350072, RussiaSearch for more papers by this authorG. D. Krapivin, G. D. Krapivin Kuban State Technol. Univ., Krasnodar 350072, RussiaSearch for more papers by this author First published: 14 October 2013 https://doi.org/10.1002/chin.201344152Read the full textAboutPDF ToolsRequest permissionExport citationAdd to favoritesTrack citation ShareShare Give accessShare full text accessShare full-text accessPlease review our Terms and Conditions of Use and check box below to share full-text version of article.I have read and accept the Wiley Online Library Terms and Conditions of UseShareable LinkUse the link below to share a full-text version of this article with your friends and colleagues. Learn more.Copy URL Share a linkShare onFacebookTwitterLinkedInRedditWechat No abstract is available for this article. Volume44, Issue44October 29, 2013 RelatedInformation

ChemInform Abstract: Three‐Component, One‐Pot Sequential Synthesis of Tetracyclic Pyrido[2′,1′:2,3]imidazo[5,1‐a]isoquinolinium Compounds as Potent Anticancer Agents.

AbstractSome of the synthesized compounds exhibit relatively strong cytotoxicity against the HeLa cell line.

Synthesis of a novel tetracyclic pyrido[3',2':4,5]thieno[3,2-b]indole system

Synthesis of a novel tetracyclic pyrido[3',2':4,5]thieno[3,2-b]indole system

Three‐Component, One‐Pot Sequential Synthesis of Tetracyclic Pyrido[2′,1′:2,3]imidazo[5,1‐a]isoquinolinium Compounds as Potent Anticancer Agents

AbstractA new practical method for the synthesis of tetracyclic pyrido[2′,1′:2,3]imidazo[5,1‐a]isoquinolinium compounds by a Yb(OTf)3/AgOTf‐catalyzed (Tf = triflate) three‐component domino reaction was developed. Significantly, the strategy presents a straightforward and efficient approach to constructing a series of compounds with potent cytotoxic activities.

Synthesis of Tetracyclic Pyrido[2,3‐b]azepine Derivatives as Analogues of Mirtazapine via N‐Acyliminium Ion Cyclization.

AbstractFor Abstract see ChemInform Abstract in Full Text.

Synthesis of Tetracyclic Pyrido[2,3-b]azepine Derivatives as Analogues of Mirtazapine via N-Acyliminium Ion Cyclization

Tetracyclic pyrido[2,3-b]azepine derivatives 4a-d and 4f as analogues of mirtazapine were synthesized via N-acyliminium ion cyclization by using aromatic rings such as benzene and thiophene ring as a <TEX>${\pi}-nucleophile$</TEX>, and evaluated for the binding affinity for <TEX>${\alpha}2-adrenoceptor$</TEX>. Among tested compounds, 2,3,9,13b-tetrahydro-1H-benzo[f]pyrrolo[2,1-a]pyrido[2,3-c]azepine (4a) was the most potent (Ki = 0.26 <TEX>${\mu}M)$</TEX> but showed about 3-fold less binding affinity than mirtazapine (Ki = 0.08 <TEX>${\mu}M)$</TEX> for a2-adrenoceptor.

Synthetic Studies of the Bioactive Natural Products by Using the Thermal Electrocyclic Reaction of 6π Electron Systems

We are developing the synthesis of biologically interesting condensed-heteroaromatic compounds, including natural products by the thermal electrocyclic reaction of 6 pi electron system incorporating the double bond of the principal aromatic or heteroaromatic ring. In this report, we describe three types of electrocyclic reactions as follows; 1) the synthesis of highly-substituted carbazole alkaloids based on the allene-mediated electrocyclic reaction involving an indole 2,3-bond, 2) the synthesis of beta-carboline alkaloids and isoquinoline-5,8-quinone alkaloids based on the thermal electrocyclic reaction of an 1-azahexatriene system involving an indole 2,3-bond or benzene 1,2-bond, and 3) the synthesis of new tetracyclic pyrido[2,3-b]indole, grossularines, based on the thermal electrocyclic of an 2-azahexatriene system including the indole 2,3-bond.

Synthesis of 1,2,3,4-tetrahydroascididemin

1,2,3,4-Tetrahydroascididemin was synthesized in six steps from 2-nitro-3,6-dimethoxy-acetophenone. The core linear tetracyclic pyrido[2,3- b]acridine system ( 6) was prepared through combination of a Friedländer reaction and an hetero Diels-Alder cycloaddition as the key steps, and the fifth ring was created using a tandem Mannich reaction-intramolecular imine formation. 1,2,3,4-Tetrahydroascididemin showed excellent in vitro antitumour activity, which was particularly selective for the human non-small cell lung cancer cell line (A-549).

Novel marine alkaloids from the tunicate Eudistoma sp. are potent regulators of cellular growth and differentiation and affect cAMP‐mediated processes

Six novel alkaloids that contain a fused tetracyclic pyrido[2,3,4-kl]acridine ring system were purified recently from the Red Sea purple tunicate Eudistoma sp. Evaluation of the effects of these alkaloids on cultured neuroblastoma and fibroblast cells revealed that they possess potent growth regulatory properties, and affect cell shape and adhesion. In mouse neuroblastoma cells, the Eudistoma alkaloids inhibited cell proliferation and induced a process of differentiation during which the cells flattened onto the surface, increased considerably in size, and extended long neurites. In hamster fibroblasts the alkaloids slowed down cell multiplication, and caused an exceptional cell flattening or elongation. In a virus-transformed derivative of the hamster fibroblasts the alkaloids restored many aspects of normal cell growth and morphology. In addition, several of the alkaloids mimicked the effects of cAMP analogs on two well-characterized cAMP-mediated processes involved in hepatic glucose metabolism--inhibition of pyruvate kinase (PK) activity and induction of mRNA for phosphoenolpyruvate carboxykinase (PEPCK). All these effects suggest that the Eudistoma alkaloids may act on the cAMP signaling system. However, a single application of these compounds was sufficient to completely block cell multiplication and to induce and sustain differentiation and "reverse transformation". Furthermore, these effects were not readily reversible following removal of the drugs. In contrast, a single application of agents that mimic or elevate cAMP induced a transient response that waned with time in culture, and the effects induced by constant elevation of cAMP reverse rapidly following drug removal. We propose that the Eudistoma alkaloids cause growth inhibition, differentiation, and reverse transformation by modifying the activity state of proteins that are involved in the regulation of cell shape and adhesion and serve as a target for the cAMP and/or other second messenger systems.