Proposed Mechanism for the Antitrypanosomal Activity of Quercetin and Myricetin Isolated from Hypericum afrum Lam.: Phytochemistry, In Vitro Testing and Modeling Studies

The in vitro activity of L. donovani (promastigotes, axenic amastigotes and intracellular amastigotes in THP1 cells) and T. brucei, from the fractions obtained from the hydroalcoholic extract of the aerial part of Hypericum afrum and the isolated compounds, has been evaluated. The chloroform, ethyl acetate and n-butanol extracts showed significant antitrypanosomal activity towards T. brucei, with IC50 values of 12.35, 13.53 and 12.93 µg/mL and with IC90 values of 14.94, 19.31 and 18.67 µg/mL, respectively. The phytochemical investigation of the fractions led to the isolation and identification of quercetin (1), myricitrin (2), biapigenin (3), myricetin (4), hyperoside (5), myricetin-3-O-β-d-galactopyranoside (6) and myricetin-3’-O-β-d-glucopyranoside (7). Myricetin-3’-O-β-d-glucopyranoside (7) has been isolated for the first time from this genus. The chemical structures were elucidated by using comprehensive one- and two-dimensional nuclear magnetic resonance (1D and 2D NMR) spectroscopic data, as well as high-resolution electrospray ionization mass spectrometry (HR-ESI–MS). These compounds have also been evaluated for their antiprotozoal activity. Quercetin (1) and myricetin (4) showed noteworthy activity against T. brucei, with IC50 and IC90 values of 7.52 and 5.71 µM, and 9.76 and 7.97 µM, respectively. The T. brucei hexokinase (TbHK1) enzyme was further explored as a potential target of quercetin and myricetin, using molecular modeling studies. This proposed mechanism assists in the exploration of new candidates for novel antitrypanosomal drugs.

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Mammalian Arginase Inhibitory Activity of Methanolic Extracts and Isolated Compounds from Cyperus Species

Molecules ◽

10.3390/molecules26061694 ◽

2021 ◽

Vol 26 (6) ◽

pp. 1694

Author(s):

Kamel Arraki ◽

Perle Totoson ◽

Alain Decendit ◽

Andy Zedet ◽

Justine Maroilley ◽

...

Keyword(s):

Inhibitory Activity ◽

Methanolic Extract ◽

Significant Inhibition ◽

Isolation And Identification ◽

Vasorelaxant Effect ◽

Methanolic Extracts ◽

Phytochemical Investigation ◽

Ic50 Values ◽

First Time

Polyphenolic enriched extracts from two species of Cyperus, Cyperus glomeratus and Cyperus thunbergii, possess mammalian arginase inhibitory capacities, with the percentage inhibition ranging from 80% to 95% at 100 µg/mL and 40% to 64% at 10 µg/mL. Phytochemical investigation of these species led to the isolation and identification of two new natural stilbene oligomers named thunbergin A-B (1–2), together with three other stilbenes, trans-resveratrol (3), trans-scirpusin A (4), trans-cyperusphenol A (6), and two flavonoids, aureusidin (5) and luteolin (7), which were isolated for the first time from C.thunbergii and C. glomeratus. Structures were established on the basis of the spectroscopic data from MS and NMR experiments. The arginase inhibitory activity of compounds 1–7 was evaluated through an in vitro arginase inhibitory assay using purified liver bovine arginase. As a result, five compounds (1, 4–7) showed significant inhibition of arginase, with IC50 values between 17.6 and 60.6 µM, in the range of those of the natural arginase inhibitor piceatannol (12.6 µM). In addition, methanolic extract from Cyperus thunbergii exhibited an endothelium and NO-dependent vasorelaxant effect on thoracic aortic rings from rats and improved endothelial dysfunction in an adjuvant-induced arthritis rat model.

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Homoadamantane and Adamantane Acylphloroglucinols from Hypericum hirsutum

Planta Medica ◽

10.1055/a-1617-7573 ◽

2021 ◽

Author(s):

Julianna Max ◽

Jörg Heilmann

Keyword(s):

Petroleum Ether Extract ◽

2D Nmr ◽

Positive Control ◽

Ionization Mass ◽

2D Nmr Spectroscopy ◽

Vitro Assay ◽

Ionization Mass Spectroscopy ◽

Ic50 Values ◽

Adamantane Skeleton

Abstract 1H NMR-guided fractionation of the petroleum ether extract of the aerial parts from Hypericum hirsutum yielded to the isolation of 19 polyprenylated polycyclic acylphloroglucinols. Structure elucidation based on 1D and 2D NMR spectroscopy together with high-resolution electrospray ionization mass spectroscopy revealed 14 acylphloroglucinols with a homoadamantane scaffold (1–14), while 5 further compounds showed an adamantane skeleton (15–19). Except for hookerione C (15), all isolated metabolites are hitherto unknown. While structurally-related metabolites have been isolated from other Hypericum species, it is the first report of admantan and homoadamantan type acylphloroglucinols in section Taeniocarpium Jaub. & Spach (Hypericaceae). The isolated compounds have been tested in a crystal violet-based in vitro assay on their properties to reduce the proliferation of human microvascular endothelial cells compared to hyperforin as the positive control. They showed a moderate reduction of proliferation with IC50 values in the range ~ 3 – 22 µM, with the homoadamantane-based compounds 2 and 4 being the most active. In addition, inhibition of the TNF-α-induced ICAM-1 expression was determined for 1 – 5, 7, and 10 – 12. Substances 3 and 12 reduced the ICAM-1 expression significantly (to 46.7% of control for 3, 62.3% for 12, at 50 µM).

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New Acyclic Cytotoxic Jasplakinolide Derivative from the Marine Sponge Jaspis splendens

Marine Drugs ◽

10.3390/md17020100 ◽

2019 ◽

Vol 17 (2) ◽

pp. 100

Author(s):

Sherif Ebada ◽

Werner Müller ◽

Wenhan Lin ◽

Peter Proksch

Keyword(s):

Spectral Analysis ◽

Marine Sponge ◽

Parent Compound ◽

2D Nmr ◽

Chemical Structures ◽

Nmr Data ◽

Ic50 Values ◽

Nanomolar Range ◽

Mouse Lymphoma

A new acylic jasplakinolide congener (2), another acyclic derivative requiring revision (4), together with two jasplakinolide derivatives including the parent compound jasplakinolide (1) were isolated from the Indonesian marine sponge Jaspis splendens. The chemical structures of the new and known compounds were unambiguously elucidated based on HRESIMS and exhaustive 1D and 2D NMR spectral analysis as well as a comparison of their NMR data with those of jasplakinolide (1). The isolated jasplakinolides inhibited the growth of mouse lymphoma (L5178Y) cells in vitro with IC50 values in the low micromolar to nanomolar range.

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Quassinoids from the Roots of Eurycoma longifolia and Their Anti-Proliferation Activities

Molecules ◽

10.3390/molecules26195939 ◽

2021 ◽

Vol 26 (19) ◽

pp. 5939

Author(s):

Wei-Qun Yang ◽

Wei Tang ◽

Xiao-Jun Huang ◽

Jian-Guo Song ◽

Yue-Yue Li ◽

...

Keyword(s):

Spectroscopic Analysis ◽

Hydroxyl Group ◽

Human Leukemia ◽

In Vitro Proliferation ◽

X Ray ◽

Eurycoma Longifolia ◽

Chemical Structures ◽

Phytochemical Investigation ◽

Ic50 Values

A phytochemical investigation on the roots of medicinal plant Eurycoma longifolia resulted in the isolation of 10 new highly oxygenated C20 quassinoids longifolactones G‒P (1–10), along with four known ones (11–14). Their chemical structures and absolute configurations were unambiguously elucidated on the basis of comprehensive spectroscopic analysis and X-ray crystallographic data. Notably, compound 1 is a rare pentacyclic C20 quassinoid featuring a densely functionalized 2,5-dioxatricyclo[5.2.2.04,8]undecane core. Compound 4 represents the first example of quassinoids containing a 14,15-epoxy functionality, and 7 features an unusual α-oriented hydroxyl group at C-14. All isolated compounds were evaluated for their anti-proliferation activities on human leukemia cells. Among the isolates, compounds 5, 12, 13, and 14 potently inhibited the in vitro proliferation of K562 and HL-60 cells with IC50 values ranging from 2.90 to 8.20 μM.

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TWO NOVEL FLAVONE C-GLYCOSIDES ISOLATED FROM AFROCARPUS GRACILIOR: POM ANALYSES AND IN VITRO CYTOTOXIC ACTIVITY AGANIST HEPATOCELLULAR CARCINOMA

International Journal of Pharmacy and Pharmaceutical Sciences ◽

10.22159/ijpps.2019v11i7.33163 ◽

2019 ◽

pp. 57-62 ◽

Cited By ~ 2

Author(s):

Amel M. Kamal ◽

Mohamed Abdelhady ◽

Taibi Ben Hadda

Keyword(s):

Hepatocellular Carcinoma ◽

Cytotoxic Activity ◽

Anticancer Agents ◽

2D Nmr ◽

Flavonoid Glycosides ◽

Ionization Mass ◽

Hep G2 ◽

Chemical Structures ◽

Pom Analyses

Objective: Cancer is considered as one of the top reasons of death and the number of cases increasing gradually. Cancer is severe clinical difficulty to the health caution system. This study explored two novel polyphenols of Afrocarpus gracilior Pilger growing in Egypt and evaluated their cytotoxic activity. Methods: Methanolic (80%) extract of the leaves of A. gracilior was subjected to column chromatography; the chemical structures of the isolated compounds were established by advanced spectral techniques: UV, 1H, 13C NMR, two dimensional NMR (2D NMR) and electron spray ionization mass spectroscopy (ESI-MS). Compounds 1 and 2 were studied for their cytotoxic activity against hepatocellular carcinoma (Hep-G2) using sulforhodamine B (SRB) assay. Furthermore the pharmacokinetics profiles of these molecules were accessed by employing Petra/Osiris/Molinspiration (POM) analyses. Results: Two novel C-flavonoid glycosides were isolated [1: Apigenin 8-C-β-D-glucopyranosyl-(1```→4``)-O-β-D-glucopyranoside] and [2: 7-O methyl-luteolin 8-C-β-glucopyranosyl-(1```→4``)-O-β-D-glucopyranoside]. They exhibited significant cytotoxic activity (IC50 = 9.02 and 15.61 µg/ml, respectively) against Hep-G2 cells. The POM analyses revealed that the activity of these two compounds depends on the presence of glucosyl and alkyl groups at the internal and terminal atmosphere of the compounds. Conclusion: These findings demonstrated that the leaves of A. gracilior contain a series of bioactive polyphenolic compounds with significant cytotoxic properties against hepatocellular carcinoma and may be used as alternative anticancer agents for doxorubicin. On the basis of POM calculations, it will be interesting to develop some alternative flavones because the deglucosylated derivatives have a better drug score than parent molecules. This preliminary study will be extended to other strains of cancer.

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Ergosterol Peroxide and Stigmasterol from The Stembark of Aglaia simplicifolia (Meliaceae) and Their Cytotoxic against HeLa Cervical Cancer Cell Lines

Jurnal Kimia VALENSI ◽

10.15408/jkv.v1i1.20068 ◽

2021 ◽

Vol 1 (1) ◽

pp. 46-51

Author(s):

Nunung Kurniasih ◽

Asep Supriadin ◽

Desi Harneti ◽

Rizky Abdulah ◽

Mohamad Nurul Azmi bin Mohamad Taib ◽

...

Keyword(s):

Cervical Cancer ◽

2D Nmr ◽

Cytotoxic Effects ◽

Cytotoxicity Activity ◽

Chemical Structures ◽

Ergosterol Peroxide ◽

Cervical Cancer Cells ◽

Ic50 Values ◽

Hela Cervical Cancer Cell

Two steroid compounds, ergosterol peroxide (1) and stigmasterol (2) have been isolated from the stembark of Aglaia simplicifolia belong to Meliaceae family. The chemical structures of 1 and 2 were identified based on spectroscopic evidence including UV, IR, 1D NMR, 2D NMR as well as mass spectra and by comparison with those previously reported spectra data. Both compounds were evaluated for their cytotoxic effects against cervical cancer HeLa cells in vitro. Compounds 1 and 2 showed cytotoxicity activity against HeLa cervical cancer cells with IC50 values of 0.80 and 26.42 µM, respectively.

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Ergosterol Peroxide and Stigmasterol from The Stembark of Aglaia simplicifolia (Meliaceae) and Their Cytotoxic against HeLa Cervical Cancer Cell Lines

Jurnal Kimia VALENSI ◽

10.15408/jkv.v7i1.20068 ◽

2021 ◽

Vol 7 (1) ◽

pp. 46-51

Author(s):

Nunung Kurniasih ◽

Asep Supriadin ◽

Desi Harneti ◽

Rizky Abdulah ◽

Mohamad Nurul Azmi bin Mohamad Taib ◽

...

Keyword(s):

Cervical Cancer ◽

2D Nmr ◽

Cytotoxic Effects ◽

Cytotoxicity Activity ◽

Chemical Structures ◽

Ergosterol Peroxide ◽

Cervical Cancer Cells ◽

Ic50 Values ◽

Hela Cervical Cancer Cell

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p-Trifluoroacetophenone Oxime Ester Derivatives: Synthesis, Antimicrobial and Cytotoxic Evaluation and Molecular Modeling Studies

Letters in Drug Design & Discovery ◽

10.2174/1570180816666181128112249 ◽

2020 ◽

Vol 17 (2) ◽

pp. 169-183 ◽

Cited By ~ 1

Author(s):

İrem Bozbey ◽

Suat Sari ◽

Emine Şalva ◽

Didem Kart ◽

Arzu Karakurt

Keyword(s):

Molecular Modeling ◽

Neuroblastoma Cell ◽

Neuroblastoma Cells ◽

Cytotoxic Agents ◽

Human Neuroblastoma Cell ◽

Human Neuroblastoma ◽

Modeling Studies ◽

Broth Microdilution Method ◽

Molecular Modeling Studies

Background: Azole antifungals are among the first-line drugs clinically used for the treatment of systemic candidiasis, a deadly type of fungal infection that threatens mostly immunecompromised and hospitalized patients. Some azole derivatives were also reported to have antiproliferative effects on cancer cells. Objective: In this study, 1-(4-trifluoromethylphenyl)-2-(1H-imidazol-1-yl)ethanone (3), its oxime (4), and a series of its novel oxime ester derivatives (5a-v) were synthesized and tested for their in vitro antimicrobial activities against certain ATCC standard strains of Candida sp. fungi and bacteria. The compounds were also tested for their cytotoxic effects against mouse fibroblast and human neuroblastoma cell lines. Molecular modeling studies were performed to provide insights into their possible mechanisms for antifungal and antibacterial actions. Methods: The compounds were synthesized by the reaction of various oximes with acyl chlorides. Antimicrobial activity of the compounds was determined according to the broth microdilution method. For the determination of cytotoxic effect, we used MTS assay. Molecular docking and QM/MM studies were performed to predict the binding mechanisms of the active compounds in the catalytic site of C. albicans CYP51 (CACYP51) and S. aureus flavohemoglobin (SAFH), the latter of which was created via homology modeling. Results: 5d, 5l, and 5t showed moderate antifungal activity against C. albicans, while 3, 5c, and 5r showed significant antibacterial activity against Staphylococcus aureus and Pseudomonas aeruginosa. Most of the compounds showed approximately 40-50% inhibition against the human neuroblastoma cells at 100 µM. In this line, 3 was the most potent with an IC50 value of 82.18 μM followed by 5a, 5o, and 5t. 3 and 5a were highly selective to the neuroblastoma cells. Molecular modelling results supported the hypothesis that our compounds were inhibitors of CAYP51 and SAFH. Conclusion: This study supports that oxime ester derivatives may be used for the development of new antimicrobial and cytotoxic agents.

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Highly Oxygenated Triterpenoids and Diterpenoids from Fructus Rubi (Rubus Chingii Hu) and Their NF-kappa B Inhibitory Effects

Molecules ◽

10.3390/molecules26071911 ◽

2021 ◽

Vol 26 (7) ◽

pp. 1911

Author(s):

Jiang Wan ◽

Xiao-Juan Wang ◽

Nan Guo ◽

Xi-Ying Wu ◽

Juan Xiong ◽

...

Keyword(s):

Inhibitory Effects ◽

Nf Kappa B ◽

Pentacyclic Triterpenoids ◽

Chemical Structures ◽

Phytochemical Investigation ◽

Ic50 Values ◽

Rubus Chingii ◽

Rubus Chingii Hu ◽

Type 3

During a phytochemical investigation of the unripe fruits of Rubus chingii Hu (i.e., Fructus Rubi, a traditional Chinese medicine named “Fu-Pen-Zi”), a number of highly oxygenated terpenoids were isolated and characterized. These included nine ursane-type (1, 2, and 4–10), five oleanane-type (3, 11–14), and six cucurbitane-type (15–20) triterpenoids, together with five ent-kaurane-type diterpenoids (21–25). Among them, (4R,5R,8R,9R,10R,14S,17S,18S,19R,20R)-2,19α,23-trihydroxy-3-oxo-urs-1,12-dien-28-oic acid (rubusacid A, 1), (2R*,4S*,5R*,8R*,9R*,10R*,14S*,17S*, 18S*,19R*,20R*)-2α,19α,24-trihydroxy-3-oxo-urs-12-en-28-oic acid (rubusacid B, 2), (5R,8R,9R,10R, 14S,17R,18S,19S)-2,19α-dihydroxy-olean-1,12-dien-28-oic acid (rubusacid C, 3), and (3S,5S,8S,9R, 10S,13R,16R)-3α,16α,17-trihydroxy-ent-kaur-2-one (rubusone, 21) were previously undescribed. Their chemical structures and absolute configurations were elucidated on the basis of spectroscopic data and electronic circular dichroism (ECD) analyses. Compounds 1 and 3 are rare naturally occurring pentacyclic triterpenoids featuring a special α,β-unsaturated keto-enol (diosphenol) unit in ring A. Cucurbitacin B (15), cucurbitacin D (16), and 3α,16α,20(R),25-tetrahydroxy-cucurbita-5,23- dien-2,11,22-trione (17) were found to have remarkable inhibitory effects against NF-κB, with IC50 values of 0.08, 0.61, and 1.60 μM, respectively.

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New quinoxalin‐1,3,4‐oxadiazole derivatives: Synthesis, characterization, in vitro biological evaluations, and molecular modeling studies

Archiv der Pharmazie ◽

10.1002/ardp.202000471 ◽

2021 ◽

Author(s):

Roghieh Mirzazadeh ◽

Mohammad S. Asgari ◽

Ebrahim Barzegari ◽

Keyvan Pedrood ◽

Maryam Mohammadi‐Khanaposhtani ◽

...

Keyword(s):

Molecular Modeling ◽

Modeling Studies ◽

Oxadiazole Derivatives ◽

Molecular Modeling Studies

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