Alkyl and Aryl Derivatives Based on <i>p</i>-Coumaric Acid Modification and Inhibitory Action against <i>Leishmania braziliensis</i> and <i>Plasmodium falciparum</i>
In low-income populations, neglected diseases are the principal cause of mortality. Of these, leishmaniasis and malaria, being parasitic, protozoan infections, affect millions of people worldwide and are creating a public health problem. The present work evaluates the leishmanicidal and antiplasmodi...
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MDPI AG
2020-07-01
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| Series: | Molecules |
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| Online Access: | https://www.mdpi.com/1420-3049/25/14/3178 |
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| author | Susiany P. Lopes Lina M. Yepes Yunierkis Pérez-Castillo Sara M. Robledo Damião P. de Sousa |
| author_facet | Susiany P. Lopes Lina M. Yepes Yunierkis Pérez-Castillo Sara M. Robledo Damião P. de Sousa |
| author_sort | Susiany P. Lopes |
| collection | DOAJ |
| description | In low-income populations, neglected diseases are the principal cause of mortality. Of these, leishmaniasis and malaria, being parasitic, protozoan infections, affect millions of people worldwide and are creating a public health problem. The present work evaluates the leishmanicidal and antiplasmodial action of a series of twelve <i>p</i>-coumaric acid derivatives. Of the tested derivatives, eight presented antiparasitic activities <b>1</b>–<b>3</b>, <b>8</b>–<b>12</b>. The hexyl <i>p</i>-coumarate derivative (<b>9</b>) (4.14 ± 0.55 μg/mL; selectivity index (SI) = 2.72) showed the highest leishmanicidal potency against the <i>Leishmania braziliensis</i> amastigote form. The results of the molecular docking study suggest that this compound inhibits aldehyde dehydrogenase (ALDH), mitogen-activated kinase protein (MPK4), and DNA topoisomerase 2 (TOP2), all of which are key enzymes in the development of <i>Leishmania braziliensis</i>. The data indicate that these enzymes interact via Van der Waals bonds, hydrophobic interactions, and hydrogen bonds with phenolic and aliphatic parts of this same compound. Of the other compounds analyzed, methyl <i>p</i>-coumarate (64.59 ± 2.89 μg/mL; IS = 0.1) demonstrated bioactivity against <i>Plasmodium falciparum</i>. The study reveals that esters presenting a <i>p</i>-coumarate substructure are promising for use in synthesis of derivatives with good antiparasitic profiles. |
| first_indexed | 2024-03-10T18:32:01Z |
| format | Article |
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| institution | Directory Open Access Journal |
| issn | 1420-3049 |
| language | English |
| last_indexed | 2024-03-10T18:32:01Z |
| publishDate | 2020-07-01 |
| publisher | MDPI AG |
| record_format | Article |
| series | Molecules |
| spelling | doaj.art-dc55f2b0d8974403b5b267e527d69f272023-11-20T06:32:15ZengMDPI AGMolecules1420-30492020-07-012514317810.3390/molecules25143178Alkyl and Aryl Derivatives Based on <i>p</i>-Coumaric Acid Modification and Inhibitory Action against <i>Leishmania braziliensis</i> and <i>Plasmodium falciparum</i>Susiany P. Lopes0Lina M. Yepes1Yunierkis Pérez-Castillo2Sara M. Robledo3Damião P. de Sousa4PostGraduation Program in Technological Development and Innovation in Medicines, Federal University of Paraíba, João Pessoa CEP 58051-970, BrazilPECET-Facultad de Medicina, Universidad de Antioquia, Medellín Calle 70 # 52-21, ColombiaEscuela de Ciencias Físicas y Matemáticas, Universidad de Las Américas, Quito 170504, EcuadorPECET-Facultad de Medicina, Universidad de Antioquia, Medellín Calle 70 # 52-21, ColombiaPostGraduation Program in Technological Development and Innovation in Medicines, Federal University of Paraíba, João Pessoa CEP 58051-970, BrazilIn low-income populations, neglected diseases are the principal cause of mortality. Of these, leishmaniasis and malaria, being parasitic, protozoan infections, affect millions of people worldwide and are creating a public health problem. The present work evaluates the leishmanicidal and antiplasmodial action of a series of twelve <i>p</i>-coumaric acid derivatives. Of the tested derivatives, eight presented antiparasitic activities <b>1</b>–<b>3</b>, <b>8</b>–<b>12</b>. The hexyl <i>p</i>-coumarate derivative (<b>9</b>) (4.14 ± 0.55 μg/mL; selectivity index (SI) = 2.72) showed the highest leishmanicidal potency against the <i>Leishmania braziliensis</i> amastigote form. The results of the molecular docking study suggest that this compound inhibits aldehyde dehydrogenase (ALDH), mitogen-activated kinase protein (MPK4), and DNA topoisomerase 2 (TOP2), all of which are key enzymes in the development of <i>Leishmania braziliensis</i>. The data indicate that these enzymes interact via Van der Waals bonds, hydrophobic interactions, and hydrogen bonds with phenolic and aliphatic parts of this same compound. Of the other compounds analyzed, methyl <i>p</i>-coumarate (64.59 ± 2.89 μg/mL; IS = 0.1) demonstrated bioactivity against <i>Plasmodium falciparum</i>. The study reveals that esters presenting a <i>p</i>-coumarate substructure are promising for use in synthesis of derivatives with good antiparasitic profiles.https://www.mdpi.com/1420-3049/25/14/3178hydroxycinnamic acidsnatural productsleishmanicidal activityantiplasmodial activitycytotoxicityneglected diseases |
| spellingShingle | Susiany P. Lopes Lina M. Yepes Yunierkis Pérez-Castillo Sara M. Robledo Damião P. de Sousa Alkyl and Aryl Derivatives Based on <i>p</i>-Coumaric Acid Modification and Inhibitory Action against <i>Leishmania braziliensis</i> and <i>Plasmodium falciparum</i> Molecules hydroxycinnamic acids natural products leishmanicidal activity antiplasmodial activity cytotoxicity neglected diseases |
| title | Alkyl and Aryl Derivatives Based on <i>p</i>-Coumaric Acid Modification and Inhibitory Action against <i>Leishmania braziliensis</i> and <i>Plasmodium falciparum</i> |
| title_full | Alkyl and Aryl Derivatives Based on <i>p</i>-Coumaric Acid Modification and Inhibitory Action against <i>Leishmania braziliensis</i> and <i>Plasmodium falciparum</i> |
| title_fullStr | Alkyl and Aryl Derivatives Based on <i>p</i>-Coumaric Acid Modification and Inhibitory Action against <i>Leishmania braziliensis</i> and <i>Plasmodium falciparum</i> |
| title_full_unstemmed | Alkyl and Aryl Derivatives Based on <i>p</i>-Coumaric Acid Modification and Inhibitory Action against <i>Leishmania braziliensis</i> and <i>Plasmodium falciparum</i> |
| title_short | Alkyl and Aryl Derivatives Based on <i>p</i>-Coumaric Acid Modification and Inhibitory Action against <i>Leishmania braziliensis</i> and <i>Plasmodium falciparum</i> |
| title_sort | alkyl and aryl derivatives based on i p i coumaric acid modification and inhibitory action against i leishmania braziliensis i and i plasmodium falciparum i |
| topic | hydroxycinnamic acids natural products leishmanicidal activity antiplasmodial activity cytotoxicity neglected diseases |
| url | https://www.mdpi.com/1420-3049/25/14/3178 |
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