scholarly journals Synthesis of 4-substituted ethers of benzophenone and their antileishmanial activities

2018 ◽  
Vol 5 (5) ◽  
pp. 171771 ◽  
Author(s):  
◽  
Faiza Ahad ◽  
Nida Ghouri ◽  
Khalid Mohammed Khan ◽  
Shahnaz Perveen ◽  
...  
Keyword(s):  
Electron Impact ◽  
Leishmania Major ◽  
Spectroscopic Techniques ◽  
Resolution Electron ◽  
Electron Impact Mass ◽  
Promastigote Form ◽  
Vector Borne ◽  
Antileishmanial Activities ◽  
Synthetic Derivatives

Leishmaniasis is a vector-borne protozoan disease; it mainly originates from the bite of sandfly and initiated when parasite is transmitted to human at metacyclic flagellated promastigote form. In the current study, a synthesis of a series of 4-substituted benzophenone ethers 1–20 was carried out in good yields and their in vitro antileishmanial activities were also screened. Among synthetic derivatives, 15 compounds 1 , 3 , 5–12 , 15 and 17 – 20 showed antileishmanial activities against promastigotes of Leishmania major with IC 50 values in the range of 1.19–82.30 µg ml −1 , and the values were compared with those of the standard pentamidine (IC 50  = 5.09 ± 0.09 µg ml −1 ). Our study identified a series of new antileishmanial molecules as potential leads. Structures of these synthetic compounds were deduced by different spectroscopic techniques, such as 1 H and 13 C nuclear magnetic resonance, electron impact and high-resolution electron impact mass spectrometry and IR.

scholarly journals Biological Activities of NHC–Pd(II) Complexes Based on Benzimidazolylidene N-heterocyclic Carbene (NHC) Ligands Bearing Aryl Substituents

Catalysts ◽  
2020 ◽  
Vol 10 (10) ◽  
pp. 1190
Author(s):  
Ibrahim Al Nasr ◽  
Nedra Touj ◽  
Waleed Koko ◽  
Tariq Khan ◽  
Ismail Özdemir ◽  
...  
Keyword(s):  
Cancer Cells ◽  
Leishmania Major ◽  
Biological Activities ◽  
Vero Cells ◽  
Spectroscopic Techniques ◽  
Biological Assays ◽  
Drug Candidates ◽  
Highly Active ◽  
Antileishmanial Activities

N-heterocyclic carbene (NHC) precursors (2a–i), their pyridine-enhanced precatalyst preparation stabilization and initiation (PEPPSI)-themed palladium N-heterocyclic carbene complexes (3a–i) and palladium N-heterocyclic triphenylphosphines complexes (4a–i) were synthesized and characterized by elemental analysis and 1H NMR, 13C NMR, IR, and LC–MS spectroscopic techniques. The (NHC)Pd(II) complexes 3–4 were tested against MCF7 and MDA-MB-231 cancer cells, Escherichia coli, methicillin-resistant Staphylococcus aureus (MRSA), Candida albicans microorganisms, Leishmania major promastigotes and amastigotes, Toxoplasma gondii parasites, and Vero cells in vitro. The biological assays indicated that all compounds are highly active against cancer cells, with an IC50 < 1.5 µg mL−1. Eight compounds proved antibacterial and antileishmanial activities, while only three compounds had strong antifungal activities against C. albicans. In our conclusion, compounds 3 (b, f, g, and h) and 4b are the most suitable drug candidates for anticancer, antimicrobial, and antiparasitical.

Antileishmanial activities of leaf latex and compound isolated from Aloe ghibensis Sebsebe & Friis

2020 ◽  
Vol 35 (1) ◽  
pp. 51-58
Author(s):  
Tamirat Tekassa ◽  
Yitagesu Tewabe ◽  
Daniel Bisrat ◽  
Asrat Hailu ◽  
Kaleab Asres
Keyword(s):  
Leishmania Donovani ◽  
Leishmania Species ◽  
2D Nmr ◽  
Antileishmanial Activity ◽  
Spectroscopic Techniques ◽  
Monocytic Cell ◽  
Monocytic Cell Line ◽  
Phytochemical Constituents ◽  
Antileishmanial Activities

Aloe ghibensis Sebsebe & Friis is traditionally used in Ethiopia for the treatment of various ailments including skin problem, wounds and malaria. Phytochemical constituents and antileshimanial properties of the leaf latex of A. ghibensis have not been reported. The objective of this study was, therefore, to determine the phytochemical constituents and in vitro antileishmanial activities of the leaf latex of A. ghibensis and its major compounds against two Leishmania species. Preparative TLC was used to isolate compounds from the leaf latex of A. ghibensis and spectroscopic techniques including 1D- and 2D-NMR as well as ESI-MS were employed to elucidate structures of the isolated compounds. In vitro antileishmanial activity was performed against promastigotes and axenically cultured amastigotes of Leishmania aethiopica and Leishmania donovani clinical isolates using Alamar Blue assay. Phytochemical investigation led to the isolation of two major anthrones, identified as aloin A/B and 7-hydroxyaloin A/B. Both the leaf latex of A. ghibensis and isolated compounds showed antileishmanial activity with IC50 values ranging from 1.6 ± 0.43 to 3.64 ± 0.09 µg/ml and 1.87 ± 0.21 to 3.72 ± 0.12 against promastigotes and axenically cultured amastigotes of L. aethopica and L. donovani, respectively. Moreover, the test substances were found to be less toxic (LC50 = 145 ± 0.72 to 156 ± 0.08 µg/ml) than amphotericin B (LC50 = 12.11 ± 0.51 µg/ml) towards human monocytic cell line (THP-1). The present study revealed that the latex and pure compounds possess genuine antileishmanial activity with high selectivity indices (SIs). Therefore, the isolated compounds can be used as a scaffold for the development of effective drugs for leishmaniasis.  

Low Resolution Electron Impact Mass Spectra of Some Quinuclidine andN-Methylpiperidine Glycolates

1980 ◽  
Vol 25 (3) ◽  
pp. 11270J ◽  
Author(s):  
Adam Vincze ◽  
Leon Gefen ◽  
Abraham Fisher ◽  
Peter Bel
Keyword(s):  
Electron Impact ◽  
Mass Spectra ◽  
Low Resolution ◽  
Resolution Electron ◽  
Electron Impact Mass ◽  
Impact Mass

scholarly journals Antileishmanial Activities of Greek Juniper (Juniperus excelsa M.Bieb.) Against Leishmania major Promastigotes

2016 ◽  
Vol 22 (1) ◽  
pp. 31-36 ◽  
Author(s):  
Mahmoodreza Moein ◽  
Gholamreza Hatam ◽  
Razieh Taghavi-Moghadam ◽  
Mohammad M. Zarshenas
Keyword(s):  
Petroleum Ether ◽  
Leaf Extract ◽  
Leishmania Major ◽  
In Vitro Toxicity ◽  
Juniperus Excelsa ◽  
The Family ◽  
Diphenyl Tetrazolium Bromide ◽  
Antileishmanial Activities ◽  
Phosphate Buffered Saline

Petroleum ether, chloroform, ethyl acetate, and n-butanol fractions of Greek juniper ( Juniperus excelsa M.Bieb. from the family Cupressaceae) were evaluated for antileishmanial activities against Leishmania major promastigotes compared to meglumine antimoniate (Glucantime). In vitro toxicity assay was performed using 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyl tetrazolium bromide and microplate ELISA reader. Extracts were prepared in ethanol/dimethyl sulfoxide (80/20) at 10 to 0.62 mg/mL. The standard was prepared in phosphate-buffered saline at 500 to 15.62 mg/mL. Both leaf and fruit extracts and related fractions showed strong inhibitory effects against promastigotes, significantly different from that of the standard. The leaf extract and the respective petroleum ether fraction showed maximum effectiveness compared to other fractions and also fruit extract and fractions (IC90 = 1.89 ± 0.03 and 0.90 ± 0.03 mg/mL, respectively). Regarding the potent activities of nonpolar fractions of Greek juniper leaf extract, these fractions can be suggested for further investigation.

scholarly journals Biodistribution and In Vivo Antileishmanial Activity of 1,2-Distigmasterylhemisuccinoyl-sn-Glycero-3-Phosphocholine Liposome-Intercalated Amphotericin B

2017 ◽  
Vol 61 (9) ◽  
Author(s):  
Maryam Iman ◽  
Zhaohua Huang ◽  
Seyedeh Hoda Alavizadeh ◽  
Francis C. Szoka ◽  
Mahmoud R. Jaafari
Keyword(s):  
Amphotericin B ◽  
Leishmania Major ◽  
Parasite Load ◽  
Tissue Concentrations ◽  
Content Type ◽  
Colloidal Properties ◽  
Covalently Linked ◽  
Antileishmanial Activities

ABSTRACT 1,2-Distigmasterylhemisuccinoyl-sn-glycero-3-phosphocholine (DSHemsPC) is a new lipid in which two molecules of stigmasterol (an inexpensive plant sterol) are covalently linked via a succinic acid to glycerophosphocholine. Our previous study revealed that liposome (Lip)-intercalated amphotericin B (AMB) prepared from DSHemsPC (DSHemsPC-AMB-Lip) possesses excellent colloidal properties and in vitro antifungal and antileishmanial activities similar to those of the liposomal AMB preparation AmBisome. The aim of this study was to determine the biodistribution and evaluate the antileishmanial effects of DSHemsPC-AMB-Lip in Leishmania major-infected BALB/c mice. The serum profile and tissue concentrations of AMB were similar in DSHemsPC-AMB-Lip- and AmBisome-treated mice after intravenous (i.v.) injection. Multiple i.v. doses of the micellar formulation of AMB (Fungizone; 1 mg/kg of body weight), DSHemsPC-AMB-Lip (5 mg/kg), and AmBisome (5 mg/kg) were used in L. major-infected BALB/c mouse models of early and established lesions. In a model of the early lesions of cutaneous leishmaniasis (CL), the results indicated that the level of footpad inflammation was significantly (P < 0.001) lower in mice treated with DSHemsPC-AMB-Lip and AmBisome than mice treated with empty liposomes or 5% dextrose. The splenic and footpad parasite load was also significantly (P < 0.001) lower in these groups of mice than in control mice that received 5% DW or free liposome. The in vivo activity of DSHemsPC-AMB-Lip was comparable to that of AmBisome, and both provided improved results compared to those achieved with Fungizone at the designated doses. The results suggest that systemic DSHemsPC-AMB-Lip administration may be useful for the treatment of leishmaniasis, and because it costs less to produce DSHemsPC-AMB-Lip than AmBisome, DSHemsPC-AMB-Lip merits further investigation.

scholarly journals Development of anEx VivoLymph Node Explant Model for Identification of Novel Molecules Active against Leishmania major

2013 ◽  
Vol 58 (1) ◽  
pp. 78-87 ◽  
Author(s):  
Alex G. Peniche ◽  
Yaneth Osorio ◽  
Adam R. Renslo ◽  
Doug E. Frantz ◽  
Peter C. Melby ◽  
...  
Keyword(s):  
Cutaneous Leishmaniasis ◽  
Leishmania Major ◽  
Drug Efficacy ◽  
Peritoneal Macrophages ◽  
Effective Concentration ◽  
Content Type ◽  
Drug Candidates ◽  
New Drug ◽  
Vector Borne

ABSTRACTLeishmaniasis is a vector-borne zoonotic infection affecting people in tropical and subtropical regions of the world. Current treatments for cutaneous leishmaniasis are difficult to administer, toxic, expensive, and limited in effectiveness and availability. Here we describe the development and application of a medium-throughput screening approach to identify new drug candidates for cutaneous leishmaniasis using anex vivolymph nodeexplantculture (ELEC) derived from the draining lymph nodes ofLeishmania major-infected mice. The ELEC supported intracellular amastigote proliferation and contained lymph node cell populations (and their secreted products) that enabled the testing of compounds within a system that mimicked the immunopathological environment of the infected host, which is known to profoundly influence parasite replication, killing, and drug efficacy. The activity of known antileishmanial drugs in the ELEC system was similar to the activity measured in peritoneal macrophages infectedin vitrowithL. major. Using the ELEC system, we screened a collection of 334 compounds, some of which we had demonstrated previously to be active againstL. donovani, and identified 119 hits, 85% of which were confirmed to be active by determination of the 50% effective concentration (EC50). We found 24 compounds (7%) that had aninvitrotherapeuticindex (IVTI; 50% cytotoxic/effective concentration [CC50]/EC50) > 100; 19 of the compounds had an EC50below 1 μM. According to PubChem searchs, 17 of those compounds had not previously been reported to be active againstLeishmania. We expect that this novel method will help to accelerate discovery of new drug candidates for treatment of cutaneous leishmaniasis.

Expression of MicroRNA of Macrophages Infected with Attenuated Leishmania major Parasite

2021 ◽  
Vol 16 (03) ◽  
pp. 106-110
Author(s):  
Mohammad Hossein Feiz Haddad ◽  
Hossein Rezvan ◽  
Alireza Nourian ◽  
Habib Habibpour
Keyword(s):  
Real Time ◽  
Leishmania Major ◽  
Host Cells ◽  
Control Group ◽  
Vector Borne Diseases ◽  
Intracellular Parasites ◽  
Significant Difference ◽  
Infected Cells ◽  
Vector Borne

Abstract Objective Leishmaniasis has been proposed as one of the neglected vector-borne diseases due to an obligate intracellular parasite of the genus Leishmania. MicroRNAs (miRNAs) with a length of 22-nucleotide are known as the noncoding small RNAs. MiRNAs contribute to many biological and cellular approaches. Therefore, the present study evaluated expressing mmu-miR-721, mmu-miR-294–3p, mmu-miR-155–3p, and mmu-miR-30a in murine macrophages infected with attenuated Leishmania major parasites on 3 days after infection. Methods Attenuated promastigotes have been achieved after 20 passages of Leishmania major parasites. Cell line J774A.1 (murine macrophage) has been used for in vitro experiments. The stationary phase of attenuated L. major promastigotes has been chosen to infect the cells, and then their incubation has been performed with 5% CO2 at 37°C for 3 days. The real-time polymerase chain reaction (PCR) has also been performed with SYBR Green master-mix Kit for measuring the level of mmu-miR-721, mmu-miR-294–3p, mmu-miR-30a, and mmu-miR-155-3p expression. Uninfected macrophages have been considered as a control group. Results Real-time PCR demonstrated overexpression of mmu-miR-155-3p, mmu-miR-294–3p, and, mmu-miR-721 in the infected cells with Leishmania parasites after 3 days. Results showed no statistically significant difference in the mmu-miR-30a expression between infected macrophages and the uninfected control group. Conclusion Our findings suggested the significant contribution of the alterations in the miRNA levels to the regulation of macrophage functions following the creation of intracellular parasites like Leishmania. These data could help to understand better the genes' expression in the host cells in the course of leishmaniasis.

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