Design, Synthesis, and Repurposing of Rosmarinic Acid-β-Amino-α-Ketoamide Hybrids as Antileishmanial Agents DOI Creative Commons
Ahmed H.E. Hassan, Waleed A. Bayoumi, Selwan M. El‐Sayed

et al.

Pharmaceuticals, Journal Year: 2023, Volume and Issue: 16(11), P. 1594 - 1594

Published: Nov. 12, 2023

A series of rosmarinic acid-β-amino-α-ketoamide hybrids were synthesized and rationally repurposed towards the identification new antileishmanial hit compounds. Two hybrids, 2g 2h, showed promising activity (IC50 values 9.5 8.8 μM against Leishmania donovani promastigotes, respectively). Their activities comparable to erufosine. In addition, cytotoxicity evaluation employing human THP-1 cells revealed that two 2h possess no cytotoxic effects up 100 µM, while erufosine possessed with CC50 value 19.4 µM. silico docking provided insights into structure–activity relationship emphasizing importance aliphatic chain at α-carbon cinnamoyl carbonyl group establishing favorable binding interactions LdCALP LARG in both 2h. light these findings, are suggested as potential safe compounds for further development anti-leishmanial agents.

Language: Английский

Development of Ag-ZnO/AgO Nanocomposites Effectives for Leishmania braziliensis Treatment DOI Creative Commons
Rafaela Miranda Barbosa, Malú Mateus Santos Obata, José Rodrigues do Carmo Neto

et al.

Pharmaceutics, Journal Year: 2022, Volume and Issue: 14(12), P. 2642 - 2642

Published: Nov. 29, 2022

Tegumentary leishmaniasis (TL) is caused by parasites of the genus Leishmania. Leishmania braziliensis (L.b) one most clinically relevant pathogens that affects skin and mucosa, causing single or multiple disfiguring life-threatening injuries. Even so, few treatment options for patients have significant toxicity, high dropout rates, cost, emergence resistant strains, which implies need studies to promote new better treatments combat disease. Zinc oxide nanocrystals are microbicidal immunomodulatory agents. Here, we develop Ag-ZnO/xAgO nanocomposites (NCPs) with three different percentages silver (AgO) (x = 49%, 65%, 68%) could act as an option tegumentary treatment. Our findings showed 65% 68% AgO inhibit extra intracellular replication L.b. present a selectivity index. Ag-ZnO/65%AgO NCPs modulate activation, expression surface receptors, cytokine production human peripheral blood mononuclear cells toward proinflammatory phenotype. These results point Ag-ZnO/AgO promising L.

Language: Английский

Citations

10
Rational repurposing, synthesis, in vitro and in silico studies of chromone-peptidyl hybrids as potential agents against Leishmania donovani DOI Creative Commons
Ahmed H.E. Hassan, Waleed A. Bayoumi, Selwan M. El‐Sayed

et al.

Journal of Enzyme Inhibition and Medicinal Chemistry, Journal Year: 2023, Volume and Issue: 38(1)

Published: June 29, 2023

A chromone-peptidyl hybrids series was synthesised and rationally repurposed towards identification of potential antileishmanial hits against visceral leishmaniasis. Three 7c, 7n, 7h showed IC50 values (9.8, 10, 12 µM, respectively) which were comparable to erufosine (9.8 µM) but lower potency than miltefosine (3.5 µM). Preliminary assessment cytotoxicity using human THP-1 cells presented 7c 7n as non-cytotoxic up 100 µM while had CC50 19.4 >40 respectively. In silico studies pinpointed the N-p-methoxyphenethyl substituent at peptidyl moiety together with oxygen-based substituted functions phenyl ring chromone crucial players in binding LdCALP. Together, these findings present anticipated hit compounds for possible development agents

Language: Английский

Citations

5
Leishmaniasis: Tissue Tropism in Relation to the Species Diversity DOI

Sanhita Ghosh,

Supriya Nath, Kamalika Roy

et al.

Published: Jan. 1, 2023

Leishmania is a vector-borne, obligatory, and anaerobic protozoan parasite that causes spectrum of clinical conditions in its hosts. The disease has several outcomes targets different parts the host body ranging from infection dermal to visceral organs. fate this depends highly on availability specific drugs their penetration into precise location pathogen residence. Unavailability medicines can caused death worldwide. This decision sustenance vs. remission various factors such as initial encounters immune system with during entry level dissemination allowed after that. turn nutritional safe residence for inside and, hence, be tropism. Therefore, understand pathogenesis, it important explore pathogen-host interactions light chapter discusses manifestations following invasion mammalian responsible them. We also summarize exceptions possible reasons including both parasitic host-related influencing outcomes.

Language: Английский

Citations

4
First-Row Transition 7-Oxo-5-phenyl-1,2,4-triazolo[1,5-a]pyrimidine Metal Complexes: Antiparasitic Activity and Release Studies DOI Creative Commons
Álvaro Martín‐Montes, Sandra Jiménez-Falcao, Santiago Gómez‐Ruiz

et al.

Pharmaceuticals, Journal Year: 2023, Volume and Issue: 16(10), P. 1380 - 1380

Published: Sept. 28, 2023

Leishmaniasis and Chagas disease are still considered neglected illnesses due to the lack of investment in research, despite fact that almost one million new cases reported every year. Four 7-oxo-5-phenyl-1,2,4-triazolo[1,5-a]pyrimidine (HftpO) first-row transition complexes (Cu, Co, Ni, Zn) have been studied for first time vitro against five different species Leishmania spp. (L. infantum, L. braziliensis, donovani, peruviana mexicana) as well Trypanosoma cruzi, showing higher efficacy than reference commercial drugs. UV luminescence properties were also evaluated. As a proof concept, anchoring model high-effective-metal complex an antiparasitic agent on silica nanoparticles was carried out time, drug-release behaviour evaluated, assessing this approach drug vehiculation.

Language: Английский

Citations

4
Design, Synthesis, and Repurposing of Rosmarinic Acid-β-Amino-α-Ketoamide Hybrids as Antileishmanial Agents DOI Creative Commons
Ahmed H.E. Hassan, Waleed A. Bayoumi, Selwan M. El‐Sayed

et al.

Pharmaceuticals, Journal Year: 2023, Volume and Issue: 16(11), P. 1594 - 1594

Published: Nov. 12, 2023

A series of rosmarinic acid-β-amino-α-ketoamide hybrids were synthesized and rationally repurposed towards the identification new antileishmanial hit compounds. Two hybrids, 2g 2h, showed promising activity (IC50 values 9.5 8.8 μM against Leishmania donovani promastigotes, respectively). Their activities comparable to erufosine. In addition, cytotoxicity evaluation employing human THP-1 cells revealed that two 2h possess no cytotoxic effects up 100 µM, while erufosine possessed with CC50 value 19.4 µM. silico docking provided insights into structure–activity relationship emphasizing importance aliphatic chain at α-carbon cinnamoyl carbonyl group establishing favorable binding interactions LdCALP LARG in both 2h. light these findings, are suggested as potential safe compounds for further development anti-leishmanial agents.

Language: Английский

Citations

4