scholarly journals SYNTHESIS, CHARACTERIZATION, AND IN VITRO ANTIMALARIAL ACTIVITY OF DIHYDROXYLATION DERIVATIVES OF TRICLOSAN

2020 ◽  
pp. 56-59
Author(s):  
WAHYU FITRIANA ◽  
ARRY YANUAR ◽  
ADE ARSIANTI ◽  
HIROKI TANIMOTO ◽  
KIYOMI KAKIUCHI
Keyword(s):  
Antimalarial Activity ◽  
Enantiomeric Excess ◽  
Vitro Assay ◽  
Therapeutic Drugs ◽  
Ofplasmodium Falciparum ◽  
Ic50 Value ◽  
Ic50 Values ◽  
New Treatment ◽  
Further Development

Objective: The emergence of malaria as a global health problem over the past few decades, accompanied by the rise of chemoresistant strains ofPlasmodium falciparum, has emphasized the need for the discovery of new therapeutic drugs against this disease. In this study, enantiomericallyenriched (enantioenriched) analogs of triclosan were synthesized and evaluated for antimalarial activity against P. falciparum cultures.Methods: Enantioselective dihydroxylation of the olefin in amide seven was performed efficiently using chiral quinine ligand (DHQ)2PHAL to yieldenantioenriched dihydroxy propionamide derivative (+)-1 in moderate yields. In a similar way, the chiral quinidine ligand (DHQD)2PHAL was used asstereoselectivity agent yielded the desired enantioenriched (−)-1. The enantioenriched products were used for further in vitro assay, and accordingly thepercent enantiomeric excess (% ee) was not determined. The structures of compounds were proven by spectral data (1H NMR, 13C NMR, and mass spectra).Results: The phenol moiety at the C1 position of triclosan was chemically substituted with a methoxy group, in conjunction with an introducedstereocenter in a 2,3-dihydroxy-propionamide group at C2’ position. Unmodified triclosan inhibited the P. falciparum cultures with an IC50 value of27.2 μM. By contrast, the triclosan analogs, compounds (+)-1 and (−)-1, inhibited the P. falciparum cultures with IC50 values of 0.034 and 0.028 μM,respectively.Conclusion: Collectively, our preliminary in vitro results suggest that these triclosan analogs have potent antimalarial activity and represent apromising new treatment strategy on further development.

scholarly journals In vitro antioxidant potency of some smaller chain glycopeptides with the prediction of IC50 values

2016 ◽  
Vol 4 (2) ◽  
pp. 127
Author(s):  
Kandasamy Nagarajan ◽  
Parul Grover ◽  
Roma Ghai ◽  
Ayushi Teharia ◽  
Sanjeev Chauhan ◽  
...  
Keyword(s):  
Hydrogen Peroxide ◽  
Ascorbic Acid ◽  
In Vitro Assay ◽  
Scavenging Activity ◽  
Vitro Assay ◽  
Standard Drug ◽  
Ic50 Value ◽  
Ic50 Values ◽  
Antioxidant Potency

Hydrogen peroxide, 1,1-Diphenyl-2-picryl-hydrazyl (DPPH) and Phosphomolybdenum in-vitro assay was employed to determine the antioxidant potency of glycopeptides RN Mannose, RK starch, RNRN Mannose and RHRCR Starch using ascorbic acid as the standard drug. The percentage scavenging activity of the glycopeptides were determined at different concentrations and the IC50 value of the test compounds were subsequently compared with that of ascorbic acid. RN Mannose was found to be most potent antioxidant compound. Also, Swiss dock study was performed with three glycopeptides, viz., RHRCR Mannose, RN Mannose and RNRN Mannose.Among these, RHRCR Mannose was found to have the best affinity for the receptor with stearic energy -0.2306kcal/mol.

scholarly journals STUDI IN VITRO POTENSI ANTIOKSIDAN DAN AKTIFITAS ANTIDIABETES FRAKSI ETIL ASETAT BUAH PARIJOTO (Medinilla speciosa B.)

2019 ◽  
Vol 12 (2) ◽  
Author(s):  
Rissa Vifta ◽  
Wilantika Wilantika ◽  
Yustisia Dian Advistasari
Keyword(s):  
Ethyl Acetate ◽  
Biological Activities ◽  
Ethyl Acetate Fraction ◽  
In Vitro Assay ◽  
Antidiabetic Activity ◽  
Vitro Assay ◽  
Antioxidants Activity ◽  
Ic50 Value ◽  
Ic50 Values

ABSTRACT Parijoto fruit (Medinilla speciosa B) contains the flavonoid which is one of the phenolic groups compounnd. Flavonoids has biological activities as anti free radical and antionxidants. The aim of this research was to evaluate the potency of ethyl acetat fraction of M.speciosa B. Extract as an antioxidants and antidiabetic. Evaluation of antioxidants activity was carried out by in vitro assay using the ABTS method (2.2 azinobis (3-ethylbenzotiazolin) -6-sulfonic acid), while the antidiabetic assay was carried out using the Nelson-Somogyi method. Research begins with the process of determination, extraction, fravtionation and contiunued by examination of each variable. The parameters of antioxidants activity was determined by IC50 values, while antidiabetic activity was measured by percentage of decreasing of glucoce levels. The results of antioxidants activity showed that ethyl acetate fraction of M. Speciosa B. had antioxidants activity with an IC50 value of 4,246 ppm with a very strong category. In line with these results, ethyl acetate fraction of M. speciosa B. had reduced glucoce levels with an optimal decrease of 50.21% a concentration of 40 ppm.   ABSTRAK Buah Parijoto (Medinilla speciosa B.) mengandung senyawa aktif flavonoid yang merupakan salah satu golongan fenolik. Flavonoid memiliki aktifitas biologis sebagai antiradikal bebas dan antioksidan. Penelitian dilakukan dengan tujuan mengetahui kemampuan fraksi etil asetat M. speciosa B sebagai antioksidan dan antidiabetes. Pengujian aktifitas antioksidan dilakukan secara in vitro dengan metode ABTS (2,2 azinobis (3-etilbenzotiazolin)-6-asam sulfonat), sedangkan uji antidiabetes dilakukan menggunakan metode Nelson-Somogyi. Penelitian diawali dengan proses determinasi, ekstraksi, fraksinasi, dan dilanjutkan dengan pengujian pada masing-masing variabel. Parameter aktifitas antioksidan diwujudkan dengan nilai IC50, sedangkan aktiftas antidiabetes diukur dengan persen penurunan kadar glukosa. Hasil pengujian aktifitas antioksidan menunjukkan bahwa fraksi etil asetat memiliki aktifitas antioksidan dengan nilai IC50 sebesar 4.14±0.08 ppm dengan kategori sangat kuat. Sejalan dengan hasil tersebut, fraksi etil asetat Buah Parijoto (M. speciosa B.) memilili kemampuan dalam menurunkan kadar glukosa dengan penurunan secara optimal sebesar 50.21±0.47% pada konsentrasi 40 ppm.    

Discovery of 3-Cinnamamido-N-Substituted Benzamides as Potential Antimalarial Agents

2020 ◽  
Vol 16 ◽  
Author(s):  
Haicheng Liu ◽  
Yushi Futamura ◽  
Honghai Wu ◽  
Aki Ishiyama ◽  
Taotao Zhang ◽  
...  
Keyword(s):  
Mammalian Cells ◽  
Antimalarial Activity ◽  
In Vitro Assays ◽  
Compound Library ◽  
Antimalarial Agents ◽  
Phenotypic Screen ◽  
Ic50 Values ◽  
Substituted Benzamides

Background: Malaria is one of the most devastating parasitic diseases, yet the discovery of antimalarial agents remains profoundly challenging. Very few new antimalarials have been developed in the past 50 years, while the emergence of drug-resistance continues to appear. Objective: This study focuses on the discovery, design, synthesis, and antimalarial evaluation of 3-cinnamamido-N-substituted benzamides. Method: In this study, a screening of our compound library was carried out against the multidrug-sensitive Plasmodium falciparum 3D7 strain. Derivatives of the hit were designed, synthesized and tested against P. falciparum 3D7 and the in vivo antimalarial activity of the most active compounds was evaluated using the method of Peters’ 4-day suppressive test. Results: The retrieved hit compound 1 containing a 3-cinnamamido-N-substituted benzamide skeleton showed moderate antimalarial activity (IC50 = 1.20 µM) for the first time. A series of derivatives were then synthesized through a simple four-step workflow, and half of them exhibited slightly better antimalarial effect than the precursor 1 during the subsequent in vitro assays. Additionally, compounds 11, 23, 30 and 31 displayed potent activity with IC50 values of approximately 0.1 µM, and weak cytotoxicity against mammalian cells. However, in vivo antimalarial activity is not effective which might be ascribed to the poor solubility of these compounds. Conclusion: In this study, phenotypic screen of our compound library resulted in the first report of 3-cinnamamide framework with antimalarial activity and 40 derivatives were then designed and synthesized. Subsequent structure-activity studies showed that compounds 11, 23, 30 and 31 exhibited the most potent and selective activity against P. falciparum 3D7 strain with IC50 values around 0.1 µM. Our work herein sets another example of phenotypic screen-based drug discovery, leading to potentially promising candidates of novel antimalarial agents once given further optimization.

Elaboration of Novel TTK1 Inhibitory Leads via QSAR-Guided Selection of Crystallographic Pharmacophores Followed By In vitro Assay

2020 ◽  
Vol 16 ◽  
Author(s):  
Mahmoud A. Al-Sha'er ◽  
Mutasem O. Taha
Keyword(s):  
Standard Error ◽  
Qsar Model ◽  
Qsar Modeling ◽  
Vitro Assay ◽  
Physicochemical Descriptors ◽  
Qsar Models ◽  
Ic50 Values ◽  
Pharmacophore Hypotheses ◽  
Selection Of

Introduction: Tyrosine threonine kinase (TTK1) is a key regulator of chromosome segregation. TTK targeting received recent concern for the enhancement of possible anticancer therapies. Objective: In this regard we employed our well-known method of QSAR-guided selection of best crystallographic pharmacophore(s) to discover considerable binding interactions that anchore inhibitors into TTK1 binding site. Method:Sixtyone TTK1 crystallographic complexes were used to extract 315 pharmacophore hypotheses. QSAR modeling was subsequently used to choose a single crystallographic pharmacophore that when combined with other physicochemical descriptors elucidates bioactivity discrepancy within a list of 55 miscellaneous inhibitors. Results: The best QSAR model was robust and predictive (r2(55) = 0.75, r2LOO = 0.72 , r2press against external testing list of 12 compounds = 0.67), Standard error of estimate (training set) (S)= 0.63 , Standard error of estimate (testing set)(Stest) = 0.62. The resulting pharmacophore and QSAR models were used to scan the National Cancer Institute (NCI) database for new TTK1 inhibitors. Conclusion: Five hits confirmed significant TTK1 inhibitory profiles with IC50 values ranging between 11.7 and 76.6 micM.

scholarly journals Antimalarial Effect of the Total Glycosides of the Medicinal Plant, Ranunculus japonicus

Pathogens ◽  
2021 ◽  
Vol 10 (5) ◽  
pp. 532
Author(s):  
Hae-Soo Yun ◽  
Sylvatrie-Danne Dinzouna-Boutamba ◽  
Sanghyun Lee ◽  
Zin Moon ◽  
Dongmi Kwak ◽  
...  
Keyword(s):  
Chinese Medicine ◽  
Traditional Chinese Medicine ◽  
Plasmodium Berghei ◽  
Antimalarial Activity ◽  
Hematological Parameters ◽  
Significant Inhibition ◽  
Ic50 Values ◽  
The Republic

In traditional Chinese medicine, Ranunculus japonicus has been used to treat various diseases, including malaria, and the young stem of R. japonicus is consumed as a food in the Republic of Korea. However, experimental evidence of the antimalarial effect of R. japonicus has not been evaluated. Therefore, the antimalarial activity of the extract of the young stem of R. japonicus was evaluated in vitro using both chloroquine-sensitive (3D7) and chloroquine-resistant (Dd2) strains; in vivo activity was evaluated in Plasmodium berghei-infected mice via oral administration followed by a four-day suppressive test focused on biochemical and hematological parameters. Exposure to extracts of R. japonicus resulted in significant inhibition of both chloroquine-sensitive (3D7) and resistant (Dd2) strains of P. falciparum, with IC50 values of 6.29 ± 2.78 and 5.36 ± 4.93 μg/mL, respectively. Administration of R. japonicus also resulted in potent antimalarial activity against P. berghei in infected mice with no associated toxicity; treatment also resulted in improved hepatic, renal, and hematologic parameters. These results demonstrate the antimalarial effects of R. japonicus both in vitro and in vivo with no apparent toxicity.

scholarly journals SYNTHESIS AND ANTIMALARIAL ACTIVITY OF SOME NEW 3-PHENYL-2-THIOXOTHIAZOLIDIN-4-ONE DERIVATIVES

2017 ◽  
Vol 9 (3) ◽  
pp. 58
Author(s):  
Mehul Zaveri ◽  
Neha Kawathekar
Keyword(s):  
Antimalarial Activity ◽  
Research Work ◽  
Aromatic Aldehydes ◽  
Maximum Activity ◽  
Spectroscopic Techniques ◽  
Activity Data ◽  
Antimalarial Agents ◽  
Ic50 Values ◽  
Current Therapies

Objective: Current therapies to treat P. falciparum malaria are heavily reliant on artemisinin-based combinations. However, resistance to artemisinin has recently been identified, and resistance to key artemisinin partner drugs is already widespread. Therefore, there is an urgent need for new antimalarial drugs with improved attributes over older therapies. The objective of this research work is to synthesize new antimalarial agents more effective against clinically relevant malarial strains.Methods: In present work, a series of ten 3-phenyl-2-thioxothiazolidin-4-one (MF1-MF10) derivatives, were synthesized by Knoevenagel condensation of N-phenyl rhodanine (I1) with substituted aromatic or hetro aromatic aldehydes using microwave irradiation. N-phenyl rhodanine (I1) was synthesized by a conventional reaction involving methyl-2-mercaptoacetate (1) and phenyl Isothiocyanates in presence of triethylamine. All the synthesized compounds were characterized by various spectroscopic techniques and evaluated for in-vitro antimalarial activity by microdilution technique against resistance strains of Plasmodium falciparum.Results: The antimalarial activity data showed that six compounds (MF1, MF3, MF4, MF5, MF7 and MF8) exhibited IC50 values ranging from 1.0-1.30 µg/ml, three compounds (MF2, MF6 and MF10) displayed IC50 values in the range of 0.9-1.0 µg/ml. Compound MF9 showed most significant result with maximum activity (IC50 = 0.85µg/ml).Conclusion: The antimalarial activity results revealed that compound MF9 possess potent activity and could be identified as a promising lead for further investigation.

scholarly journals Inhibition of Heme Polymerization Invitro Assay Of Extract of Sirih Leaf (Piper betle Linn.) and Sun Flower Leaves (Helianthus annuus L.)

2020 ◽  
Vol 7 (1) ◽  
pp. 22 ◽  
Author(s):  
Ami Tjitraresmi ◽  
Moelyono Moektiwardoyo ◽  
Yasmiwar Susilawati
Keyword(s):  
Helianthus Annuus ◽  
Antimalarial Activity ◽  
Antimalarial Drugs ◽  
Piper Betle ◽  
Phytochemical Screening ◽  
Helianthus Annuus L ◽  
Betel Leaf ◽  
The People ◽  
Ic50 Values

Malaria is a disease that occurs in tropical countries like Indonesia. The incidence of malaria in the world is still quite high and the occurrence of cases of Plasmodium resistance to antimalarial drugs and the widespread of resistance have prompted researchers to look for new antimalarial drugs, especially from natural materials. Betel leaf (Piper betle Linn.) And sunflower leaf (Helianthus annuus L.) have long been used by the people of Indonesia as an antimalarial drug. The purpose of this study was to determine antimalarial activity through inhibition of heme polymerization and determine secondary metabolite compounds by phytochemical screening from betel leaves and sunflower leaves. The heme polymerization inhibition activity assay was carried out by the in-vitro method using a microplate reader at 415 nm and 630 nm wavelengths. IC50 values of betel leaf extract and sunflower leaf were 178.67 μg/ml and 160.10 μg/ml, respectively. Phytochemical screening results from betel leaf showed the presence of flavonoids, polyphenols, tannins, quinones, saponins, and monoterpenoids-sesquiterpenoids, while sunflower leaves contain alkaloids, polyphenols, flavonoids, steroids and monoterpenoids-sesquiterpenoids.Keywords: Piper betle Linn., Helianthus annuus L., Malaria, Heme Polymerization

Steroid Compounds Isolation from Carthamus tinctorius Linn as Antimalarial

2021 ◽  
pp. 5297-5304
Author(s):  
Rini Hamsidi ◽  
Wahyuni Wahyuni ◽  
Adryan Fristiohady ◽  
Muhammad Hajrul Malaka ◽  
Idin Sahidin ◽  
...  
Keyword(s):  
Antimalarial Activity ◽  
Carthamus Tinctorius ◽  
Spectroscopic Techniques ◽  
1H And 13C Nmr ◽  
Marker Compound ◽  
Ic50 Value ◽  
Ft Ir ◽  
Ir Spectroscopic

Carthamus tinctorius Linn, also known as safflower, is a plant with the potential of being used in the production of antimalarial drugs. The purpose of this study was to isolate and identify the steroid compounds in the safflower and determine its antimalarial activity in vitro. The isolation process was conducted through extraction and chromatography methods. Then, the characterization of the isolated compounds was conducted through spectroscopic techniques which include Fourier Transform Infrared Spectroscopy (FT-IR), NMR 1-D (1H and 13C-NMR), and NMR 2-D (HMQC, HMBC, and H-H COZY) as well as comparing data with the existing literatures. In addition, the tests conducted were with variations of isolate concentrations (10, 1, 0.1, 0.01, and 0.001 μg/mL) against 3D7 strain of Plasmodium falciparum. Based on the FT-IR spectroscopic data, the steroid compounds isolated from safflowers might be stigmasterols. In addition, the isolates had -OH functional group in the region of 3431 cm-1, C-O in the region of 1053 cm-1, and Csp3-H in regions of 2960, 2934, and 2865 cm-1. The NMR 1-D data showed presence of 29 carbon atoms, while the protons were 48 in number. Furthermore, the IC50 value of the compound was 34.03 μg/mL with a percentage inhibition of 43.92% against the growth of P. falciparum. Therefore, it was classified as inactive agent in inhibiting the growth of malaria parasites, however, it could be used as a marker compound in C. tinctorius Linn extract.

Homoadamantane and Adamantane Acylphloroglucinols from Hypericum hirsutum

Planta Medica ◽  
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).

Antimalaria Activity of Cassia spectabilis DC Leaf and Its Inhibition Effect in Heme Detoxification

2020 ◽  
Author(s):  
Wiwied - Ekasari ◽  
Dewi Resty Basuki ◽  
Heny - Arwati ◽  
Tutik Sri Wahy
Keyword(s):  
Antimalarial Activity ◽  
Ethanol Extract ◽  
Ic50 Value ◽  
Cassia Spectabilis ◽  
In Vivo Testing ◽  
Chloroquine Diphosphate ◽  
Better Than

Abstract Background In previous studies, Cassia spectabilis DC leaf has shown a good antimalarial activity. Therefore, this study is a follow-up study of leaf activity and mechanism of C. spectabilis DC as an antimalarial. Methods In vitro antimalarial activity testing using P. falciparum which was done with bioassay guide isolation in order to obtain the active compound. In vivo testing towards infected P. berghei mice was conducted to determine the effects of antimalarial prophylaxis and antimalarial activity in combination with artesunate. Whereas, heme detoxification inhibition testing as one of the antimalarial mechanisms was carried out using the Basilico method. Results The results showed that active antimalarial isolate obtained from C. spectabilis DC leaf had a structural pattern that was identical to (-)-7-hydroxyspectaline. Prophylactic test on infected P. berghei mice obtained the highest dose of inhibition percentage of 90% ethanol extract of C. spectabilis DC leaf was 68.61% while positive (doxycycline) control at 100 mg kg-1 was 73.54%. In antimalarial testing in combination with artesunate, it was found that administering 150 mg kg-1 (three times a day) of C. spectabilis DC (D0 − D2) + artesunate (D2) was better than the standard combination of amodiaquine + artesunate with 99.18% and 92.88% inhibition percentage. For the inhibitory activity of heme detoxification from ethanol extract 90%, C. spectabilis DC leaf had IC50 value of 0.375 mg mL-1 which was better than chloroquine diphosphate. Conclusion These results showed that C. spectabilis DC leaves possesses potent antimalarial activity and may offer a potential agent for effective and affordable antimalarial phytomedicine.

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