Theoretical study of new LmDHODH and LmTXNPx complexes: structure-based relationships
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ORIGINAL RESEARCH
Theoretical study of new LmDHODH and LmTXNPx complexes: structure-based relationships Plinio Cantero-López 1,2 & Sara M. Robledo Restrepo 3 & Osvaldo Yañez 4,5,6 & César Zúñiga 7,8 & Gilmar G. Santafé-Patiño 9 Received: 14 July 2020 / Accepted: 20 August 2020 # Springer Science+Business Media, LLC, part of Springer Nature 2020
Abstract In this work, a series of eight novel ring-substituted styrylquinolines were synthesized, and in silico physicochemical properties were estimated. The inhibitory activity of these compounds was evaluated in intracellular amastigotes of Leishmania (Viannia) panamensis, and their affinity for L. major dihydroorotate dehydrogenase DHODH (LmDHODH) and L. major tryparedoxin peroxidase TXNPx (LmTXNPx) was calculated by molecular docking, NCI index, and the recently developed IGM analysis, providing us useful insights about the forces governing the ligand-protein coupling. The eight synthesized molecules do not break the Lipinski, Ghose, Veber, Egan, and Muegge rules. Therefore, the bioavailability and absorption will not be poor. Keywords Leishmania (Viannia) panamensis . NCI index . ADMET properties . Molecular modeling . Ring-substituted styrylquinolines
Introduction During the last decades, the parasitic disease leishmaniasis has become one of the biggest health problems worldwide, causing approximately 50,000 deaths every year and exposing over 20 billion people to contagium [1, 2]. Leishmaniasis is generated by intracellular protozoan parasites of the genus
Leishmania (Leishmania spp.), which are transferred to mammals, including men, by the bite of females infected with phlebotomous insects of the genus Lutzomya, Phlebotumus, and Psychodopygus. The main forms of clinical manifestations are cutaneous, mucous, and visceral. The symptons can include several skin and mucosal ulcers, anemia, fever, and death [3]. The trypanosomatid protozoa Leishmania is
Electronic supplementary material The online version of this article (https://doi.org/10.1007/s11224-020-01624-7) contains supplementary material, which is available to authorized users. * Plinio Cantero-López [email protected]; [email protected] 1
Relativistic Molecular Physics Group (ReMoPh), PhD program in Molecular Physical Chemistry, Facultad de Ciencias Exactas, Universidad Andres Bello, República 275, Santiago, Chile
5
Center for Bioinformatics and Integrative Biology (CBIB), Facultad de Ciencias de la Vida, Universidad Andres Bello, Av. Republica ́ 330, 8370146 Santiago, Chile
6
Center of New Drugs for Hypertension (CENDHY), Santiago, Chile
7
Instituto de Ciencias Naturales, Facultad de Medicina Veterinaria y Agronomía, Universidad de Las Américas, Sede Providencia, Manuel Montt 948, 7500972 Santiago, Chile
2
Center of Applied Nanoscience (CANS), Facultad de Ciencias Exactas, Universidad Andres Bello, Av. República 330, Santiago, Chile
3
PECET-Programa de Estudio y Control de Enfermedades Tropicales. Facultad de Medicina, Universidad de Antioquia, Calle 70 No. 52– 21, Medellín A
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