In vitro antileishmanial activity of novel azoles (3-imidazolylflavanones) against promastigote and amastigote stages of Leishmania major
Copyright © 2016 Elsevier B.V. All rights reserved..
Leishmaniasis is a protozoan infectious disease widely distributed all around the world. First line drugs including antimoniales are insufficient due to resistance in endemic areas and high toxicity. Azole antifungals like ketoconazole (KCZ) are also used as antileishmanial agents for several decades. In the present study, we evaluated in vitro antileishmanial effects of new azole antifungals namely 3-imidazolylflavanones (IFs) and their oximes (IFOs) against Leishmania major (L. major) parasites. The obtained results showed remarkable effect of our compounds on promastigote and amastigote stages of L. major. In particular, the 4-chloro analog of flavanone (IF-2) and 3-chloro substituted flavanone oxime (IFO-3) with IC50 values ≤8.9μg/mL were 8-fold more potent than KCZ (IC50=72μg/mL) against promastigote form of L. major. In amastigote stage, the compounds IF-2 and IFO-2 decreased the mean number of infected macrophages (MIR) more than KCZ (p<0.005). In addition, compounds IF-1, IF-2, IF-4, IFO-2, IFO-3 and IFO-5 decreased the mean number of amastigotes per macrophages (MNAPM) significantly more than KCZ (p<0.005). All compounds decreased both MIR and MNAPM significantly more than control (p<0.001). Compounds IF-2 and IFO-2 with parasite survival of 7.70% and 20% had the highest inhibition on intracellular amastigotes. Although most of compounds displayed acceptable selectivity index, compound IF-2 had the highest CC50 value (115.4μg/mL) and SI (383.3). We concluded that our new synthetic azoles displaying potent activity against L. major could be considered as new hits for drug development in the field of antileishmanial therapy.
| Medienart: |
E-Artikel |
|---|
| Erscheinungsjahr: |
2017 |
|---|---|
| Erschienen: |
2017 |
| Enthalten in: |
Zur Gesamtaufnahme - volume:167 |
|---|---|
| Enthalten in: |
Acta tropica - 167(2017) vom: 30. März, Seite 73-78 |
| Sprache: |
Englisch |
|---|
| Beteiligte Personen: |
Shokri, Azar [VerfasserIn] |
|---|
| Links: |
|---|
| Themen: |
Amastigote |
|---|
| Anmerkungen: |
Date Completed 23.02.2017 Date Revised 11.03.2022 published: Print-Electronic Citation Status MEDLINE |
|---|
| doi: |
10.1016/j.actatropica.2016.12.027 |
|---|
| funding: |
|
|---|---|
| Förderinstitution / Projekttitel: |
|
| PPN (Katalog-ID): |
NLM267462166 |
|---|
| LEADER | 01000naa a22002652 4500 | ||
|---|---|---|---|
| 001 | NLM267462166 | ||
| 003 | DE-627 | ||
| 005 | 20231224220733.0 | ||
| 007 | cr uuu---uuuuu | ||
| 008 | 231224s2017 xx |||||o 00| ||eng c | ||
| 024 | 7 | |a 10.1016/j.actatropica.2016.12.027 |2 doi | |
| 028 | 5 | 2 | |a pubmed24n0891.xml |
| 035 | |a (DE-627)NLM267462166 | ||
| 035 | |a (NLM)28017860 | ||
| 035 | |a (PII)S0001-706X(16)30440-5 | ||
| 040 | |a DE-627 |b ger |c DE-627 |e rakwb | ||
| 041 | |a eng | ||
| 100 | 1 | |a Shokri, Azar |e verfasserin |4 aut | |
| 245 | 1 | 0 | |a In vitro antileishmanial activity of novel azoles (3-imidazolylflavanones) against promastigote and amastigote stages of Leishmania major |
| 264 | 1 | |c 2017 | |
| 336 | |a Text |b txt |2 rdacontent | ||
| 337 | |a ƒaComputermedien |b c |2 rdamedia | ||
| 338 | |a ƒa Online-Ressource |b cr |2 rdacarrier | ||
| 500 | |a Date Completed 23.02.2017 | ||
| 500 | |a Date Revised 11.03.2022 | ||
| 500 | |a published: Print-Electronic | ||
| 500 | |a Citation Status MEDLINE | ||
| 520 | |a Copyright © 2016 Elsevier B.V. All rights reserved. | ||
| 520 | |a Leishmaniasis is a protozoan infectious disease widely distributed all around the world. First line drugs including antimoniales are insufficient due to resistance in endemic areas and high toxicity. Azole antifungals like ketoconazole (KCZ) are also used as antileishmanial agents for several decades. In the present study, we evaluated in vitro antileishmanial effects of new azole antifungals namely 3-imidazolylflavanones (IFs) and their oximes (IFOs) against Leishmania major (L. major) parasites. The obtained results showed remarkable effect of our compounds on promastigote and amastigote stages of L. major. In particular, the 4-chloro analog of flavanone (IF-2) and 3-chloro substituted flavanone oxime (IFO-3) with IC50 values ≤8.9μg/mL were 8-fold more potent than KCZ (IC50=72μg/mL) against promastigote form of L. major. In amastigote stage, the compounds IF-2 and IFO-2 decreased the mean number of infected macrophages (MIR) more than KCZ (p<0.005). In addition, compounds IF-1, IF-2, IF-4, IFO-2, IFO-3 and IFO-5 decreased the mean number of amastigotes per macrophages (MNAPM) significantly more than KCZ (p<0.005). All compounds decreased both MIR and MNAPM significantly more than control (p<0.001). Compounds IF-2 and IFO-2 with parasite survival of 7.70% and 20% had the highest inhibition on intracellular amastigotes. Although most of compounds displayed acceptable selectivity index, compound IF-2 had the highest CC50 value (115.4μg/mL) and SI (383.3). We concluded that our new synthetic azoles displaying potent activity against L. major could be considered as new hits for drug development in the field of antileishmanial therapy | ||
| 650 | 4 | |a Journal Article | |
| 650 | 4 | |a Amastigote | |
| 650 | 4 | |a Antileishmanial agents | |
| 650 | 4 | |a Azole antifungals | |
| 650 | 4 | |a Flavanones | |
| 650 | 4 | |a Leishmania major | |
| 650 | 4 | |a Promastigote | |
| 650 | 7 | |a Antiprotozoal Agents |2 NLM | |
| 650 | 7 | |a Flavanones |2 NLM | |
| 650 | 7 | |a Imidazoles |2 NLM | |
| 650 | 7 | |a Oximes |2 NLM | |
| 700 | 1 | |a Emami, Saeed |e verfasserin |4 aut | |
| 700 | 1 | |a Fakhar, Mahdi |e verfasserin |4 aut | |
| 700 | 1 | |a Teshnizi, Saeed Hosseini |e verfasserin |4 aut | |
| 700 | 1 | |a Keighobadi, Masoud |e verfasserin |4 aut | |
| 773 | 0 | 8 | |i Enthalten in |t Acta tropica |d 1945 |g 167(2017) vom: 30. März, Seite 73-78 |w (DE-627)NLM000025097 |x 1873-6254 |7 nnns |
| 773 | 1 | 8 | |g volume:167 |g year:2017 |g day:30 |g month:03 |g pages:73-78 |
| 856 | 4 | 0 | |u http://dx.doi.org/10.1016/j.actatropica.2016.12.027 |3 Volltext |
| 912 | |a GBV_USEFLAG_A | ||
| 912 | |a GBV_NLM | ||
| 951 | |a AR | ||
| 952 | |d 167 |j 2017 |b 30 |c 03 |h 73-78 | ||