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Synthesis, In Silico Studies, Antiprotozoal and Cytotoxic Activities of Quinoline‐Biphenyl Hybrids
Author(s) -
Coa Juan Carlos,
Yepes Andrés,
Carda Miguel,
ConesaMilián Laura,
Upegui Yulieth,
Robledo Sara M.,
CardonaG Wilson
Publication year - 2020
Publication title -
chemistryselect
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.437
H-Index - 34
ISSN - 2365-6549
DOI - 10.1002/slct.201903835
Subject(s) - antiprotozoal , trypanosoma cruzi , in silico , quinoline , benznidazole , chemistry , miltefosine , docking (animal) , stereochemistry , biochemistry , leishmania donovani , biology , pharmacology , leishmaniasis , in vitro , organic chemistry , parasite hosting , medicine , nursing , world wide web , computer science , visceral leishmaniasis , immunology , gene
The synthesis, in silico studies, antiprotozoal and cytotoxic activities of eleven quinoline‐biphenyl hybrids are described herein. The structure of the synthesized products was elucidated by a combination of spectrometric analyses. The synthesized compounds were evaluated against Plasmodium falciparum, and amastigotes forms both Leishmania (V) panamensis and Trypanosoma cruzi . Cytotoxicity was evaluated against human U‐937 macrophages. 8‐phenylquinoline ( 4 a ) showed similar activity than meglumine antimoniate and 4‐(quinolin‐8‐yl)phenol ( 4 b ) exhibited an activity similar to that of benznidazole. 8‐(3,4‐dimethoxyphenyl) quinoline ( 4 k ) showed the best activity against P. falciparum . Although these compounds were toxic for mammalian U‐937 cells, however they may still have potential to be considered as candidates for drug development because of their antiparasite activity. Molecular docking was used to determine the in silico inhibition of some of the designed compounds against PfLDH and cruzipain, two important pharmacological targets involved in antiparasitic diseases. All hybrids were docked to the three‐dimensional structures of PfLDH and T. cruzi cruzipain as enzymes using AutoDock Vina. Notably, the docking results showed that the most active compounds 4‐(quinolin‐8‐yl)phenol ( 4 b , CE 50 : 11.33 μg/mL for T. cruzi ) and 8‐(3,4‐dimethoxyphenyl) quinoline ( 4 k , CE 50 : 8.84 μg/mL for P. falciparum ) exhibited the highest scoring pose (−7.5 and −7.7 kcal/mol, respectively). This result shows a good correlation between the predicted scores with the experimental data profile, suggesting that these ligands could act as competitive inhibitors of Pf LDH or T. cruzi cruzipain enzymes, respectively. Finally, in silico ADME studies of the quinoline hybrids showed that these novel compounds have suitable drug‐like properties, making them potentially promising agents for antiprotozoal therapy.