Facile synthesis of 1,2,3-triazole-fused indolo- and pyrrolo[1,4]diazepines, DNA-binding and evaluation of their anticancer activity.

Synthèse aisée d'indolo- et pyrrolo[1,4]diazépines condensées à un 1,2,3-triazole, liaison à l'ADN et évaluation de leur activité anticancéreuse.

Clicks: 314
ID: 57919
2019
Article Quality & Performance Metrics
Overall Quality
Not rated
Combines reader engagement with the AI quality analysis. This article has not been analysed, so there is no overall score — reader engagement is measured and shown alongside.
AI Quality Assessment
Not analyzed
Readership in this journal
Steady

Ranked #64 of 133 articles by views in Bioorganic chemistry

Most read Least read

Bar heights use a square-root scale. Only the 120 most-read articles are drawn; the journal has 133 in total.

Mint this article as an NFT
Not yet minted

Create a permanent, verifiable on-chain record of this article on the Scimatic Network. The NFT is held in your Journament account, and you can withdraw it to your own wallet at any time.

5 SUSD one-off · no wallet required
Sign in to mint
Abstract
A facile synthetic strategy has been developed for the generation of structurally diverse N-fused heterocycles. The formation of fused 1,2,3-triazole indolo and pyrrolodiazepines proceeds through an initial Knoevenagel condensation followed by intramolecular azide-alkyne cycloaddition reaction at room temperature without recourse to the traditional Cu(I)-catalyzed azide-alkyne cycloadditions. The synthesized compounds were evaluated for their in vitro anti-cancer activity against the NCI 60 cell line panel. Among the tested compounds, 3a and 3h were found to exhibit potent inhibitory activity against many of the cell lines. Cell cycle analysis indicated that the compounds inhibit the cell cycle at sub G1 phase. The DNA- nano drop method, viscosity experiment and docking studies suggested these compounds possess DNA binding affinity.
Une stratégie de synthèse aisée a été développée pour la préparation d'hétérocycles N-condensés structuralement diversifiés. La formation d'indolo- et de pyrrolodiazépines condensées à un cycle 1,2,3-triazole s'effectue par une condensation initiale de Knoevenagel, suivie d'une réaction de cycloaddition azoture-alcyne intramoléculaire à température ambiante, sans recourir aux traditionnelles cycloadditions azoture-alcyne catalysées par le Cu(I). L'activité anticancéreuse *in vitro* des composés synthétisés a été évaluée sur le panel de 60 lignées cellulaires du NCI. Parmi les composés testés, 3a et 3h ont montré une puissante activité inhibitrice contre un grand nombre de ces lignées cellulaires. L'analyse du cycle cellulaire a indiqué que ces composés inhibent le cycle cellulaire en phase sub-G1. La méthode NanoDrop appliquée à l'ADN, les expériences de viscosimétrie et les études d'amarrage moléculaire suggèrent que ces composés possèdent une affinité de liaison à l'ADN.
Foi desenvolvida uma estratégia sintética simples para a geração de heterociclos N-fundidos estruturalmente diversos. A formação de indolo- e pirrolodiazepinas fundidas a 1,2,3-triazol ocorre por meio de uma condensação inicial de Knoevenagel, seguida por uma reação de cicloadição azida-alcino intramolecular à temperatura ambiente, sem a necessidade das tradicionais cicloadições azida-alcino catalisadas por Cu(I). Os compostos sintetizados foram avaliados quanto à sua atividade antitumoral *in vitro* frente ao painel de 60 linhagens celulares do NCI. Dentre os compostos testados, verificou-se que 3a e 3h exibem potente atividade inibitória contra muitas das linhagens celulares. A análise do ciclo celular indicou que os compostos inibem o ciclo celular na fase sub-G1. O método de NanoDrop para DNA, o ensaio de viscosidade e os estudos de docagem molecular sugeriram que esses compostos possuem afinidade de ligação ao DNA.
Reference Key
gour2019facilebioorganic Use this key to autocite in the manuscript while using SciMatic Manuscript Manager or Thesis Manager
Authors Jitendra Gour, Srikanth Gatadi, Venkatesh Pooladanda, Shaik Mahammad Ghouse, Satyaveni Malasala, Y V Madhavi, Chandraiah Godugu, Srinivas Nanduri
Are you one of these authors? Claim your profile
Journal Bioorganic chemistry
Year 2019
DOI
S0045-2068(19)31025-9
URL
Keywords
Cytotoxicity dna-binding fused polycyclics mda-mb-468 cancer cells

Citations

No citations found. To add a citation, contact the admin at info@scimatic.org

Comments

No comments yet. Be the first to comment on this article.