Leishmanicidal and cytotoxic activities and 4D‐QSAR of 2‐arylidene indan‐1,3‐diones
| Autor: | Gustavo Costa Bressan, Wallace Pacienza Lima, Bartira Rossi Bergmann, Róbson Ricardo Teixeira, Maria Paula Gonçalves Borsodi, Maria Cristina Andreazza Costa, Graziela Domingues de Almeida Lima, Alex R. Aguiar, Márcia M. C. Ferreira, Ana Paula Martins de Souza |
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| Rok vydání: | 2021 |
| Předmět: |
Quantitative structure–activity relationship
Leukemia Chemistry Stereochemistry HL60 Leishmania mexicana Antiprotozoal Agents Quantitative Structure-Activity Relationship Pharmaceutical Science Antineoplastic Agents HL-60 Cells Biological activity Inhibitory Concentration 50 Benzonitrile chemistry.chemical_compound Cell Line Tumor Indans Drug Discovery Humans Cytotoxic T cell Organic synthesis Cytotoxicity IC50 |
| Zdroj: | Archiv der Pharmazie. 354:2100081 |
| ISSN: | 1521-4184 0365-6233 |
| DOI: | 10.1002/ardp.202100081 |
| Popis: | The indan-1,3-dione and its derivatives are important building blocks in organic synthesis and present important biological activities. Herein, the leishmanicidal and cytotoxicity evaluation of 16 2-arylidene indan-1,3-diones is described. The compounds were evaluated against the leukemia cell lines HL60 and Nalm6, and the most effective ones were 2-(4-nitrobenzylidene)-1H-indene-1,3(2H)-dione (4) and 4-[(1,3-dioxo-1H-inden-2(3H)-ylidene)methyl]benzonitrile (10), presenting IC50 values of around 30 µmol/L against Nalm6. The leishmanicidal activity was assessed on Leishmania amazonensis, with derivative 4 (IC50 = 16.6 µmol/L) being the most active. A four-dimensional quantitative structure-activity analysis (4D-QSAR) was applied to the indandione derivatives, through partial least-squares regression. The statistics presented by the regression models built with the selected field descriptors of Coulomb (C) and Lennard-Jones (L) nature, considering the activities against L. amazonensis, HL60, and Nalm6 leukemia cells, were, respectively, R2 = 0.88, 0.92, and 0.98; Q2 = 0.83, 0.88, and 0.97. The presence of positive Coulomb descriptors near the carbonyl groups indicates that these polar groups are related to the activities. Besides, the presence of positive Lennard-Jones descriptors close to substituents R3 or R1 indicates that bulky nonpolar substituents in these positions tend to increase the activities. This study provides useful insights into the mode of action of indandione derivatives for each biological activity involved. |
| Databáze: | OpenAIRE |
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