One-Pot Multicomponent Synthesis of Methoxybenzo[h]quinoline-3-carbonitrile Derivatives; Anti-Chagas, X-ray, and In Silico ADME/Tox Profiling Studies
| Autor: | Mario V. Capparelli, Katiuska Charris, Jorge Angel, Benjamín Nogueda-Torres, Esteban Fernandez-Moreira, Jaime Charris, Hegira Ramírez |
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| Jazyk: | angličtina |
| Rok vydání: | 2021 |
| Předmět: |
Trypanosoma cruzi
One-pot synthesis Pharmaceutical Science Organic chemistry Article Analytical Chemistry Acetic acid chemistry.chemical_compound Structure-Activity Relationship QD241-441 Drug Discovery methoxybenzo[h]quinoline medicine one-pot synthesis Humans cancer Chagas Disease Computer Simulation Physical and Theoretical Chemistry Nifurtimox ADME Malononitrile Quinoline chagas Combinatorial chemistry Trypanocidal Agents chemistry Chemistry (miscellaneous) Benznidazole Drug Design Quinolines Molecular Medicine Ammonium acetate medicine.drug |
| Zdroj: | Molecules, Vol 26, Iss 6977, p 6977 (2021) Molecules |
| ISSN: | 1420-3049 |
| Popis: | Several methoxybenzo[h]quinoline-3-carbonitrile analogs were designed and synthesized in a repositioning approach to developing compounds with anti-prostate cancer and anti-Chagas disease properties. The compounds were synthesized through a sequential multicomponent reaction of aromatic aldehydes, malononitrile, and 1-tetralone in the presence of ammonium acetate and acetic acid (catalytic). The effect of the one-pot method on the generation of the target product has been studied. The compounds were in vitro screened against bloodstream trypomastigotes of T. cruzi (NINOA and INC-5 strains) and were most effective at showing a better activity profile than nifurtimox and benznidazole (reference drugs). A study in silico on absorption, distribution, metabolism, excretion, and toxicity (ADME/Tox) profiling to help describe the molecular properties related to the pharmacokinetic aspects in the human body of these compounds was reported. In addition, X-ray data for the compound 2-Amino-5,6-dihydro-4-(3-hydroxy-4-methoxy-phenyl)-8-methoxybenzo[h]quinoline-3-carbonitrile 6 was being reported. Spectral (IR, NMR, and elemental analyses) data on all final compounds were consistent with the proposed structures. |
| Databáze: | OpenAIRE |
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