In Vitro Antileishmanial and Antischistosomal Activities of Anemonin Isolated from the Fresh Leaves of Ranunculus multifidus Forsk

Leishmaniasis and schistosomiasis are neglected tropical diseases (NTDs) infecting the world’s poorest populations. Effectiveness of the current antileishmanial and antischistosomal therapies are significantly declining, which calls for an urgent need of new effective and safe drugs. In Ethiopia fresh leaves of Ranunculus multifidus Forsk. are traditionally used for the treatment of various ailments including leishmaniasis and eradication of intestinal worms. In the current study, anemonin isolated from the fresh leaves of R. multifidus was assessed for its in vitro antileishmanial and antischistosomal activities. Anemonin was isolated from the hydro-distilled extract of the leaves of R. multifidus. Antileishmanial activity was assessed on clinical isolates of the promastigote and amastigote forms of Leishmania aethiopica and L. donovani clinical isolates. Resazurin reduction assay was used to determine antipromastigote activity, while macrophages were employed for antiamastigote and cytotoxicity assays. Antischistosomal assays were performed against adult Schistosoma mansoni and newly transformed schistosomules (NTS). Anemonin displayed significant antileishmanial activity with IC50 values of 1.33 nM and 1.58 nM against promastigotes and 1.24 nM and 1.91 nM against amastigotes of L. aethiopica and L. donovani, respectively. It also showed moderate activity against adult S. mansoni and NTS (49% activity against adult S. mansoni at 10 µM and 41% activity against NTS at 1 µM). The results obtained in this investigation indicate that anemonin has the potential to be used as a template for designing novel antileishmanial and antischistosomal pharmacophores.

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Potential Antileishmanial Activity of Essential Oils of Native Species from Southern Brazil

Environment and Natural Resources Research ◽

10.5539/enrr.v6n4p18 ◽

2016 ◽

Vol 6 (4) ◽

pp. 18 ◽

Cited By ~ 2

Author(s):

Carla Kauffmann ◽

Eduardo M. Ethur ◽

Barbara Buhl ◽

Talita Scheibel ◽

Gerzia M. C. Machado ◽

...

Keyword(s):

Essential Oils ◽

Native Species ◽

Neglected Tropical Diseases ◽

Antileishmanial Activity ◽

Reference Drug ◽

Ic50 Values ◽

Brazilian Flora ◽

South Of Brazil ◽

Antileishmanial Activities

Leishmaniasis are a neglected tropical diseases that affecting 98 countries on three continents. Every year, 1.3 million of people are infected with the disease and 50.000 persons die because of this. The aim of this work was to evaluate antileishmanial activities in vitro from native species of South of Brazil belonging to the Myrtaceae family. The essential oils from leaves of Calyptranthes grandifolia, Calyptranthes tricona, Eugenia anomala, Eugenia arenosa, Eugenia pyriformis, Myrrhinium atropurpureum and Psidium salutare were analyzed in vitro for antileishmanial activity against promastigotes of Leishmania amazonensis, employed MTT assay. The essential oils from leaves of C. grandifolia, C. tricona, E. arenosa and E. pyriformis presented IC50 values of 31.27 ± 6.40 µg/mL, 26.13 ± 8.60 µg/mL, 13.72 ± 8.65 µg/mL and 19.73 ± 5.40 µg/mL, respectively, and not are statistically different from pentamidine (IC50 = 23.22 ± 9.04 µg/mL), the reference drug. The results show the potential of essential oils from leaves of C. grandifolia, C. tricona, E. arenosa and E. pyriformis as antileishmanial, as well as the importance of continuing studies to in order to advance in the search and development of new therapeutic options from of brazilian flora sources.

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In vitro antileishmanial activity of Anacardium othonianum and isolated compounds against Leishmania amazonensis

Acta Brasiliensis ◽

10.22571/2526-4338429 ◽

2021 ◽

Vol 5 (1) ◽

pp. 44

Author(s):

Tavane Aparecida Alvarenga ◽

Osvaine Júnior Alvarenga Alves ◽

Mariana Cintra Pagotti ◽

Wilson Roberto Cunha ◽

Márcio Luís Andrade e Silva ◽

...

Keyword(s):

High Resolution Mass Spectrometry ◽

Leishmania Amazonensis ◽

Antileishmanial Activity ◽

Anacardic Acid ◽

Array Detector ◽

Preparative Hplc ◽

Moderate Activity ◽

Phytochemical Study ◽

Phenol Derivatives

This study analyzes the antileishmanial activity of the crude ethanol extract, fractions, and isolated compounds of A. othonianum nuts. Antileishmanial activity was evaluated against Leishmania amazonensis promastigotes in vitro. The phytochemical study was performed by high-performance liquid chromatography-high-resolution mass spectrometry-diode array detector (HPLC-HRMS-DAD) and by preparative HPLC. HPLC-HRMS-DAD analysis of the bioactive extract confirmed the presence of ten alkyl phenol derivatives that had previously been isolated from A. occidentale. Bioassay-guided isolation afforded cardanol triene, cardanol diene, cardanol monoene, cardol triene, anacardic acid triene, anacardic acid diene, and anacardic acid monoene. Cardol triene gave an IC50 of 80.66 µM. The obtained data suggest that the evaluated extract, fractions, and cardol triene had moderate activity against L. amazonensis promastigotes. This is the first description of alkyl phenols in A. othonianum.

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In Vitro Activity of Ibrexafungerp against a Collection of Clinical Isolates of Aspergillus, Including Cryptic Species and Cyp51A Mutants, Using EUCAST and CLSI Methodologies

Journal of Fungi ◽

10.3390/jof7030232 ◽

2021 ◽

Vol 7 (3) ◽

pp. 232

Author(s):

Olga Rivero-Menendez ◽

Juan Carlos Soto-Debran ◽

Manuel Cuenca-Estrella ◽

Ana Alastruey-Izquierdo

Keyword(s):

Cryptic Species ◽

Antifungal Susceptibility ◽

Sensu Stricto ◽

Vitro Activity ◽

Clinical Isolates ◽

Moderate Activity ◽

In Vitro Activity ◽

Synthesis Inhibitor ◽

Complex Species

Ibrexafungerp is a new orally-available 1,3-β-D-glucan synthesis inhibitor in clinical development. Its in vitro activity and that of amphotericin B, voriconazole, and micafungin were evaluated against a collection of 168 clinical isolates of Aspergillus spp., including azole–susceptible and azole–resistant (Cyp51A mutants) Aspergillus fumigatus sensu stricto (s.s.) and cryptic species of Aspergillus belonging to six species complexes showing different patterns of antifungal resistance, using EUCAST and CLSI antifungal susceptibility testing reference methods. Ibrexafungerp displayed low geometric means of minimal effective concentrations (MECs) against A. fumigatus s.s. strains, both azole susceptible (0.040 mg/L by EUCAST and CLSI versus 1.231 mg/L and 0.660 mg/L for voriconazole, respectively) and azole resistant (0.092 mg/L and 0.056 mg/L, EUCAST and CLSI, while those for voriconazole were 2.144 mg/L and 2.000 mg/L). Ibrexafungerp was active against most of the cryptic species of Aspergillus tested, yielding MEC values only comparable to those of micafungin. Nevertheless, this new compound exhibited a moderate activity against A. ustus complex species, MECs ≥ 0.5 mg/L against Aspergillus insuetus and Aspergillus keveii strains, and was inactive against the Aspergillus alliaceus isolates tested (MEC90s ≥ 16 mg/L). All in all, ibrexafungerp shows encouraging in vitro results against cryptic species of Aspergillus and azole–susceptible and azole resistant strains of A. fumigatus, some of which are difficult to treat using the available therapeutic options.

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Computer-aided structural optimization, synthesis, evaluation of the antimicrobial and cytotoxic activity of some pyrazoline derivatives

MedPharmRes ◽

10.32895/ump.mpr.6.1.6 ◽

2021 ◽

Vol 6 (1) ◽

pp. 33-39

Author(s):

Tai Duc Nguyen ◽

Du Nguyen Hai Ly ◽

Thi Hong Tuoi Do ◽

Phuong Thi Ngoc Huynh

Keyword(s):

Antimicrobial Activity ◽

Anticancer Activity ◽

Antibacterial Activities ◽

Dilution Method ◽

Agar Dilution Method ◽

Moderate Activity ◽

Docking Model ◽

Ic50 Values ◽

Relationship Of

Introduction: In the last few decades, pyrazoline-based substances have emerged as potential antimicrobial and anticancer candidates. In concern with antimicrobial activity, this study aims to build a docking model to predict the structure of potential 2-pyrazoline derivatives. The cytotoxicity of some compounds was also evaluated to get insight into the structure–anticancer activity relationship of the 2-pyrazoline derivatives. Methods: Docking models were built on virtual FabH enzymes using FlexX platform with 2-pyrazoline derivatives served as test sets. Afterward, derivatives with high docking scores were chemically synthesized and evaluated for antibacterial activity using the agar dilution method. Furthermore, MTT assay was used to assess the cytotoxicity of these compounds. Results: The docking score and the in vitro minimum inhibitory concentration (MIC) value on Staphylococcus aureus (S. aureus) bacteria strongly correlate with an R-square value of 0.6751 (p < 0.0001). Four 2 pyrazoline derivatives were synthesized and evaluated for antimicrobial activity. Their MIC values on S. aureus range between 4 and 16 μg/mL, consistent with ones predicted by the docking model. Apropos cytotoxic properties, a series of 2-pyrazolines exhibit a moderate activity on HepG2, RD, and MDA-MB-231. The most active compound, HP10, has the IC50 values on these cell lines. which are 26.62 μM, 17.74 μM, 14.47 μM, respectively. Conclusion: Our research built a docking model on the virtual S. aureus FabH enzyme with high potential in predicting antibacterial activities of different 2-pyrazoline derivatives. Moreover, our cytotoxicity results provided data for further studies on the anticancer activity of these promising derivatives.

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Antileishmanial Activity of Diterpene lactones from Suregada multiflora and Their Semisynthetic Derivatives

Current Bioactive Compounds ◽

10.2174/1573407214666180516101031 ◽

2020 ◽

Vol 16 (1) ◽

pp. 53-57

Author(s):

Humaira Y. Gondal ◽

Muhammad Nisar ◽

Muhammad I. Choudhary

Keyword(s):

Brine Shrimp ◽

Low Cost ◽

Alternative Therapy ◽

Protozoan Parasite ◽

Structural Diversity ◽

Chemotherapeutic Agents ◽

Antileishmanial Activity ◽

Cytotoxic Effects ◽

Ic50 Values

Background: There is a general lack of effective and economical chemotherapeutic agents for the treatment of widely prevalent leishmanias. To develop locally available, low cost alternative therapy, a series of diterpene lactones isolated from Suregada multiflora and their semisynthetic derivatives have been evaluated against the protozoan parasite Leishmania. Methods: A series of diterpene lactones were isolated from methanolic extract of Suregada multiflora. Major constituents were further derivatized through chemical and microbial transformations. Antileishmanial activity of structurally diverse diterpene lactones was performed by testing them in vitro against L. donovani promastigotes. All compounds were also tested for their cytotoxic effects by the brine shrimp bioassay. Results: Among all compounds evaluated in current studies, natural diterpenes Gelomulide A (1) and G (2) were found significantly active with IC50 values below 20µg/ml. While, among synthesized derivatives; compounds 5, 9 and 10 were found more potent with IC50 value 17.49, 18.38 and 17.81µg/ml, respectively. None of these compounds showed cytotoxic effects in the brine shrimp bioassay (LC50> 300). Conclusion: A new class of diterpene lactones was identified as potential antileshmanial agent. The structural diversity of natural and semisynthetic diterpene lactones, helped to rationalize structure– activity relationships. Activity of these diterpene lactones owed to C-8/14 epoxide along with unsubstituted C-1. Keto group at C-1 always lower the activity unless it is in α, β-unsaturated form. Presence of acetyl group at C-3 and 6 usually augmented the antileishmanila potential

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Synthesis and Antileishmanial Activity of 1,2,4,5-Tetraoxanes against Leishmania donovani

Molecules ◽

10.3390/molecules25030465 ◽

2020 ◽

Vol 25 (3) ◽

pp. 465 ◽

Cited By ~ 2

Author(s):

Lília I. L. Cabral ◽

Sébastien Pomel ◽

Sandrine Cojean ◽

Patrícia S. M. Amado ◽

Philippe M. Loiseau ◽

...

Keyword(s):

Leishmania Donovani ◽

Parasite Burden ◽

Selectivity Index ◽

Antileishmanial Activity ◽

Diverse Range ◽

Ic50 Value ◽

Ic50 Values ◽

Antileishmanial Drug ◽

Intraperitoneal Treatment

A chemically diverse range of novel tetraoxanes was synthesized and evaluated in vitro against intramacrophage amastigote forms of Leishmania donovani. All 15 tested tetraoxanes displayed activity, with IC50 values ranging from 2 to 45 µm. The most active tetraoxane, compound LC140, exhibited an IC50 value of 2.52 ± 0.65 µm on L. donovani intramacrophage amastigotes, with a selectivity index of 13.5. This compound reduced the liver parasite burden of L. donovani-infected mice by 37% after an intraperitoneal treatment at 10 mg/kg/day for five consecutive days, whereas miltefosine, an antileishmanial drug in use, reduced it by 66%. These results provide a relevant basis for the development of further tetraoxanes as effective, safe, and cheap drugs against leishmaniasis.

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In Vitro Activities of Bedaquiline and Delamanid against Nontuberculous Mycobacteria Isolated in Beijing, China

Antimicrobial Agents and Chemotherapy ◽

10.1128/aac.00031-19 ◽

2019 ◽

Vol 63 (8) ◽

Cited By ~ 3

Author(s):

Xia Yu ◽

XiaoPan Gao ◽

Chenghai Li ◽

Jingjing Luo ◽

Shuan Wen ◽

...

Keyword(s):

Nontuberculous Mycobacteria ◽

Antimicrobial Activities ◽

Clinical Isolates ◽

Natural Resistance ◽

Pharmacokinetic Data ◽

Moderate Activity ◽

Content Type ◽

Long Course ◽

Reference Strains

ABSTRACT Due to the natural resistance of nontuberculous mycobacteria (NTM) against multiple antibiotics, treatment of infections caused by them is often long-course and less successful. The main objective of our study was the evaluation of in vitro susceptibility of 209 isolates consisting of different NTM species against bedaquiline and delamanid. Furthermore, reference strains of 33 rapidly growing mycobacterium (RGM) species and 19 slowly growing mycobacterium (SGM) species were also tested. Bedaquiline exhibited strong in vitro activity against both reference strains and clinical isolates of different SGM species, as the majority of the strains demonstrated MICs far below 1 μg/ml. Bedaquiline (Bdq) also exhibited potent activity against the recruited RGM species. A total of 29 out of 33 reference RGM strains had MICs lower than 1 μg/ml. According to the MIC distributions, the tentative epidemiological cutoff (ECOFF) values, and the pharmacokinetic data, a uniform breakpoint of 2 μg/ml was temporarily proposed for NTM’s Bdq susceptibility testing. Although delamanid (Dlm) was not active against most of the tested reference strains and clinical isolates of RGM species, it exhibited highly variable antimicrobial activities against the 19 tested SGM species. Eleven species had MICs lower than 0.25 μg/ml, and 7 species had MICs greater than 32 μg/ml. Large numbers of M. kansasii (39/45) and M. gordonae (6/10) clinical isolates had MICs of ≤0.125 μg/ml. This study demonstrated that bedaquiline had potent activity against different NTM species in vitro, and delamanid had moderate activity against certain species of SGM. The data provided important insights on the possible clinical application of Bdq and Dlm to treat NTM infections.

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Indane-1,3-diones: as potential and selective α-glucosidase inhibitors, their synthesis, in vitro and in silico studies.

Medicinal Chemistry ◽

10.2174/1573406416666200826102051 ◽

2020 ◽

Vol 16 ◽

Author(s):

Asma Mukhtar ◽

Shazia Shah ◽

Kanwal ◽

Shehryar Hameed ◽

Khalid Mohammed Khan ◽

...

Keyword(s):

In Silico ◽

Binding Mode ◽

Docking Studies ◽

Moderate Activity ◽

Spectroscopic Techniques ◽

In Silico Docking ◽

In Silico Studies ◽

Synthetic Molecules ◽

Ic50 Values

Background: Diabetes mellitus is one the most chronic metabolic disorder. Since past few years our research group had synthesized and evaluated libraries of heterocyclic compounds against α and β-glucosidase enzymes and found encouraging results. The current study comprises of evaluation of indane-1,3-dione as antidiabetic agents based on our previously reported results obtained from closely related moiety isatin and its derivatives. Objective: A library of twenty three indane-1,3-dione derivatives (1-23) was synthesized and evaluated for α and βglucosidase inhibitions. Moreover, in silico docking studies were carried out to investigate the putative binding mode of selected compounds with the target enzyme. Method: The indane-1,3-dione derivatives (1-23) were synthesized by Knoevenagel condensation of different substituted benzaldehydes with indane-1,3-dione under basic condition. The structures of synthetic molecules were deduced by using different spectroscopic techniques including 1H-, 13C-NMR, EI-MS, and CHN analysis. Compounds (1-23) were evaluated for α and β-glucosidase inhibitions by adopting the literature protocols. Result: Off twenty three, eleven compounds displayed good to moderate activity against α-glucosidase enzyme, nonetheless, all compounds exhibited less than 50% inhibition against β-glucosidase enzyme. Compounds 1, 14, and 23 displayed good activity against α-glucosidase enzyme with IC50 values of 2.80 ± 0.11, 0.76 ± 0.01, and 2.17 ± 0.18 µM, respectively. The results have shown that these compounds have selectively inhibited the α-glucosidase enzyme. The in silico docking studies also supported the above results and showed different types of interactions of synthetic molecules with the active site of enzyme. Conclusion: The compounds 1, 14, and 23 have shown good inhibition against α-glucosidase and may potentially serve as lead for the development of new therapeutic representatives.

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Antimicrobial and Antileishmanial Activities of Hypocrellins A and B

Antimicrobial Agents and Chemotherapy ◽

10.1128/aac.48.11.4450-4452.2004 ◽

2004 ◽

Vol 48 (11) ◽

pp. 4450-4452 ◽

Cited By ~ 90

Author(s):

Guoyi Ma ◽

Shabana I. Khan ◽

Melissa R. Jacob ◽

Babu L. Tekwani ◽

Zuqiang Li ◽

...

Keyword(s):

Antimicrobial Activities ◽

Antileishmanial Activity ◽

In Vivo Studies ◽

Moderate Activity ◽

Structure Activity ◽

Hypocrellin A ◽

Hypocrellin B ◽

Antileishmanial Activities

ABSTRACT Hypocrellins A and B were evaluated for in vitro antimicrobial and antileishmanial activities. Hypocrellin A exhibited promising activity against Candida albicans and moderate activity against Staphylococcus aureus, methicillin-resistant S. aureus, Pseudomonas aeruginosa, and Mycobacterium intracellulare. Hypocrellin B showed weak antimicrobial activities. Hypocrellin A exhibited potent antileishmanial activity, while hypocrellin B was only moderately active. These results of promising antifungal and antileishmanial activity of hypocrellin A may be useful for further structure-activity relationship and in vivo studies.

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Bioguided Isolation of Cyclopenin Analogues as Potential SARS-CoV-2 Mpro Inhibitors from Penicillium citrinum TDPEF34

Biomolecules ◽

10.3390/biom11091366 ◽

2021 ◽

Vol 11 (9) ◽

pp. 1366

Author(s):

Bathini Thissera ◽

Ahmed M. Sayed ◽

Marwa H. A. Hassan ◽

Sayed F. Abdelwahab ◽

Ngozi Amaeze ◽

...

Keyword(s):

Hydrophobic Interactions ◽

Structural Information ◽

Positive Control ◽

Penicillium Citrinum ◽

Moderate Activity ◽

Enzyme Active Site ◽

Drug Candidates ◽

Ic50 Values

SARS-CoV-2 virus mutations might increase its virulence, and thus the severity and duration of the ongoing pandemic. Global drug discovery campaigns have successfully developed several vaccines to reduce the number of infections by the virus. However, finding a small molecule pharmaceutical that is effective in inhibiting SARS-CoV-2 remains a challenge. Natural products are the origin of many currently used pharmaceuticals and, for this reason, a library of in-house fungal extracts were screened to assess their potential to inhibit the main viral protease Mpro in vitro. The extract of Penicillium citrinum, TDPEF34, showed potential inhibition and was further analysed to identify potential Mpro inhibitors. Following bio-guided isolation, a series of benzodiazepine alkaloids cyclopenins with good-to-moderate activity against SARS-CoV-2 Mpro were identified. The mode of enzyme inhibition of these compounds was predicted by docking and molecular dynamic simulation. Compounds 1 (isolated as two conformers of S- and R-isomers), 2, and 4 were found to have promising in vitro inhibitory activity towards Mpro, with an IC50 values range of 0.36–0.89 µM comparable to the positive control GC376. The in silico investigation revealed compounds to achieve stable binding with the enzyme active site through multiple H-bonding and hydrophobic interactions. Additionally, the isolated compounds showed very good drug-likeness and ADMET properties. Our findings could be utilized in further in vitro and in vivo investigations to produce anti-SARS-CoV-2 drug candidates. These findings also provide critical structural information that could be used in the future for designing potent Mpro inhibitors.

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