Synthesis and Evaluation of in vitro Antiplatelet Aggregation Activities of 2-Methoxy-5-Aminobenzamides

2019 ◽  
Vol 16 (9) ◽  
pp. 1040-1050
Author(s):  
Lili Liu ◽  
Xiujie Liu ◽  
Guangling Chen ◽  
Kai Qiu
Keyword(s):  
L929 Cells ◽  
Cytotoxicity Activity ◽  
Antiplatelet Aggregation ◽  
Ic50 Value ◽  
Lower Effect ◽  
New Compounds ◽  
Group Characteristics ◽  
Better Than ◽  
Methoxybenzoic Acid

Objective: According to the principles of drug design, the structures of picotamide and betrixaban were combined to design novel series of 2-methoxy-5-aminobenzamides. A total of twenty new compounds 1a-1t have been synthesized and evaluated for their antiplatelet aggregation activities in vitro. Methods: In the structural design of target compounds 1a-1t, the betrixaban was retained group characteristics and the picotamide was retained its 1, 3, 4-substitution position. With 2-methoxybenzoic acid as starting material, compounds 1a-1t were synthesized after 5 steps of nitration, acylation, ammoniation, reduction and secondary ammoniation. And their antiplatelet aggregation activities in vitro were assessed by the Born test with ADP, arachidonic acid and collagen as inducing agents, respectively, and with aspirin and picotamide as two reference drugs. Results: The compound 1f (46.14%±0.07) had the highest activity for ADP and its IC50 value was 0.17 µM, far better than the two control drugs aspirin (0.44 µM) and picotamide (0.47 µM). The IC50 value of four compounds 1i (0.24 µM), 1j (0.22 µM), 1r (0.25 µM) and 1t (0.24 µM), displayed higher antiplatelet activities in vitro for AA than aspirin (0.43 µM) and picotamide (0.34 µM). Evaluation of cytotoxicity activity of the compounds against L929 cells line revealed that at lower concentration of 10 µmol·L-1, compound 1p had lower effect on L929 cells, and its cell survival rate (88.24%±4.16) was higher than that (82.35%±4.16) of picotamide. Conclusion: Novel series of 2-methoxy-5-aminobenzamides has shown higher in vitro antiplatelet activities and lower effect on L929 cells at lower concentration.

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.

scholarly journals Design, Synthesis and Biological Evaluation of Novel 4-Substituted Coumarin Derivatives as Antitumor Agents

Molecules ◽  
2018 ◽  
Vol 23 (9) ◽  
pp. 2281 ◽  
Author(s):  
Ran An ◽  
Zhuang Hou ◽  
Jian-Teng Li ◽  
Hao-Nan Yu ◽  
Yan-Hua Mou ◽  
...  
Keyword(s):  
Antitumor Agents ◽  
Cancer Cell Line ◽  
Biological Evaluation ◽  
Design Synthesis ◽  
Hypoxic Conditions ◽  
Ca Ix ◽  
Ic50 Value ◽  
Almost All ◽  
New Compounds

Herein, fifteen new compounds containing coumarin, 1,2,3-triazole and benzoyl- substituted arylamine moieties were designed, synthesized and tested in vitro for their anticancer activity. The results showed that all tested compounds had moderate antiproliferative activity against MDA-MB-231, a human breast cancer cell line, under both normoxic and hypoxic conditions. Furthermore, the 4-substituted coumarin linked with benzoyl 3,4-dimethoxyaniline through 1,2,3-triazole (compound 5e) displayed the most prominent antiproliferative activities with an IC50 value of 0.03 μM, about 5000 times stronger than 4-hydroxycoumarin (IC50 > 100 μM) and 20 times stronger than doxorubicin (IC50 = 0.60 μM). Meanwhile, almost all compounds revealed general enhancement of proliferation-inhibiting activity under hypoxia, contrasted with normoxia. A docking analysis showed that compound 5e had potential to inhibit carbonic anhydrase IX (CA IX).

scholarly journals Screening and Application of Chitin Synthase Inhibitors

Processes ◽  
2020 ◽  
Vol 8 (9) ◽  
pp. 1029
Author(s):  
Xiaozai Shi ◽  
Shuo Qiu ◽  
Yingling Bao ◽  
Hanchi Chen ◽  
Yuele Lu ◽  
...  
Keyword(s):  
Antifungal Activity ◽  
Inhibitory Concentration ◽  
Inhibitory Effect ◽  
Chitin Synthase ◽  
Fungal Cell ◽  
Ic50 Value ◽  
Further Development ◽  
Fungicide Target ◽  
Better Than

Chitin is an important part of the fungal cell wall, but is not found in plants and mammals, so chitin synthase (CHS) can be a green fungicide target. In this paper, 35 maleimide compounds were designed and synthesized as CHS inhibitors. All the screened compounds showed different degrees of CHS inhibitory activity and antifungal activity in vitro. In particular, the half–inhibitory concentration (IC50) value of compound 20 on CHS was 0.12 mM, and the inhibitory effect was better than that of the control polyoxin B (IC50 = 0.19 mM). At the same time, this compound also showed good antifungal activity and has further development value.

scholarly journals Design, Synthesis, andIn VitroAntiplatelet Aggregation Activities of Ferulic Acid Derivatives

2015 ◽  
Vol 2015 ◽  
pp. 1-7 ◽  
Author(s):  
Peng-Xuan Zhang ◽  
Hang Lin ◽  
Cheng Qu ◽  
Yu-Ping Tang ◽  
Nian-Guang Li ◽  
...  
Keyword(s):  
Ferulic Acid ◽  
Target Compound ◽  
Design Synthesis ◽  
Antiplatelet Aggregation ◽  
Aggregation Activity ◽  
New Compounds

In order to discover new compounds with antiplatelet aggregation activities, some ferulic acid (FA) derivatives were designed and synthesized. Thein vitroantiplatelet aggregation activities of these compounds were assessed by turbidimetric test. The results showed that the target compound7fhad potent antiplatelet aggregation activity with its IC5027.6 μmol/L, and7fcan be regarded as a novel potent antiplatelet aggregation candidate.

scholarly journals Novel Thiosemicarbazone Derivatives: In Vitro and In Silico Evaluation as Potential MAO-B Inhibitors

Molecules ◽  
2021 ◽  
Vol 26 (21) ◽  
pp. 6640
Author(s):  
Derya Osmaniye ◽  
Berkant Kurban ◽  
Begüm Nurpelin Sağlık ◽  
Serkan Levent ◽  
Yusuf Özkay ◽  
...  
Keyword(s):  
Inhibitory Activity ◽  
Active Sites ◽  
Docking Study ◽  
Fluorometric Method ◽  
Mao B ◽  
Micromolar Concentration ◽  
Ic50 Value ◽  
Competitive Inhibitors ◽  
New Compounds

MAO-B inhibitors are frequently used in the treatment of neurodegenerative diseases such as Parkinson’s and Alzheimer’s. Due to the limited number of compounds available in this field, there is a need to develop new compounds. In the recent works, it was shown that various thiosemicarbazone derivatives show hMAO inhibitory activity in the range of micromolar concentration. It is thought that benzofuran and benzothiophene structures may mimic structures such as indane and indanone, which are frequently found in the structures of such inhibitors. Based on this view, new benzofuran/benzothiophene and thiosemicarbazone hybrid compounds were synthesized, characterized and screened for their hMAO-A and hMAO-B inhibitory activity by an in vitro fluorometric method. The compounds including methoxyethyl substituent (2b and 2h) were found to be the most effective agents in the series against MAO-B enzyme with the IC50 value of 0.042 ± 0.002 µM and 0.056 ± 0.002 µM, respectively. The mechanism of hMAO-B inhibition of compounds 2b and 2h was investigated by Lineweaver–Burk graphics. Compounds 2b and 2h were reversible and non-competitive inhibitors with similar inhibition features as the substrates. The Ki values of compounds 2b and 2h were calculated as 0.035 µM and 0.046 µM, respectively, with the help of secondary plots. The docking study of compound 2b and 2h revealed that there is a strong interaction between the active sites of hMAO-B and analyzed compound.

Triterpenoids with Antiplatelet Aggregation Activity from the Roots of Ilex pubescens

Planta Medica ◽  
2016 ◽  
Vol 83 (09) ◽  
pp. 797-804 ◽  
Author(s):  
Qinglong Tan ◽  
Maosong Qiu ◽  
Di Cao ◽  
Tianqin Xiong ◽  
Lei Zhang ◽  
...  
Keyword(s):  
Platelet Aggregation ◽  
Adenosine Diphosphate ◽  
Significant Inhibition ◽  
Triterpene Saponins ◽  
Rabbit Plasma ◽  
Antiplatelet Aggregation ◽  
Aggregation Activity ◽  
Ilex Pubescens ◽  
New Compounds

AbstractTwo new triterpenes and five new triterpene saponins, named ilexpusons A–G (1–7), as well as eight known compounds were isolated from Ilex pubescens. The structures of the new compounds were established by a combination of chemical and spectroscopic methods, including HRESIMS, 1H-NMR, 13C-NMR, 1H-1H COSY, HSQC, HMBC, and NOESY. Additionally, the biological activity of compounds 1 – 15 against adenosine diphosphate-induced platelet aggregation in rabbit plasma was determined. Among the tested compounds, 1, 2, 5, 6, 8, 13, 14, and 15 exhibited significant inhibition of platelet aggregation in vitro.

Integration of Bioinformatics and in vitro Analysis Reveal Anti-leishmanial Effects of Azithromycin and Nystatin

2019 ◽  
Vol 14 (5) ◽  
pp. 450-459
Author(s):  
Irum Jehangir ◽  
Syed Farhan Ahmad ◽  
Maryam Jehangir ◽  
Anwar Jamal ◽  
Momin Khan
Keyword(s):  
In Silico ◽  
Dosage Form ◽  
Antifungal Drugs ◽  
Pure Form ◽  
Potential Candidate ◽  
Leishmania Tropica ◽  
Ic50 Value ◽  
Antibacterial And Antifungal ◽  
Better Than

Background: Leishmaniasis is the major cause of mortality in under-developed countries. One of the main problems in leishmaniasis is the limited number of drug options, resistance and side effects. Such a situation requires to study the new chemical series with anti-leishmanial activity. Objective: To assess the anti-leishmanial activity of antibacterial and antifungal drugs. Methods: We have applied an integrative approach based on computational and in vitro methods to elucidate the efficacy of different antibacterial and antifungal drugs against Leishmania tropica (KWH23). Firstly these compounds were analyzed using in silico molecular docking. This analysis showed that the nystatin and azithromycin interacted with the active site amino acids of the target protein leishmanolysin. The nystatin, followed by azithromycin, produced the lowest binding energies indicating their inhibitive activity against the target. The efficacy of the docked drugs was further validated in vitro which showed that our bioinformatics based predictions completely agreed with experimental results. Stock solutions of drugs, media preparation and parasites cultures were performed according to the standard in-vitro protocol. Results: We found that the half maximal inhibitory concentration (IC50) value of dosage form of nystatin (10,000,00 U) and pure nystatin was 0.05701 µM and 0.00324 µM respectively. The IC50 value of combined azithromycin and nystatin (dosage and pure form) was 0.156 µg/ml and 0.0023 µg /ml (0.00248 µM) respectively. It was observed that IC50 value of nystatin is better than azithromycin and pure form of drugs had significant activity than the dosage form of drugs. Conclusion: From these results, it was also proven that pure drugs combination result is much better than all tested drugs results. The results of both in vitro and in silico studies clearly indicated that comparatively, nystatin is the potential candidate drug in combat against Leishmania tropica.

scholarly journals Prenylated Diphenyl Ethers from the Marine Algal-Derived Endophytic Fungus Aspergillus tennesseensis

Molecules ◽  
2018 ◽  
Vol 23 (9) ◽  
pp. 2368 ◽  
Author(s):  
Zhao-Xia Li ◽  
Xiu-Fang Wang ◽  
Guang-Wei Ren ◽  
Xiao-Long Yuan ◽  
Ning Deng ◽  
...  
Keyword(s):  
Endophytic Fungus ◽  
Diphenyl Ether ◽  
Antimicrobial Activities ◽  
Cytotoxic Activities ◽  
Ic50 Value ◽  
Diphenyl Ethers ◽  
Marine Algal ◽  
Spectroscopy Studies ◽  
New Compounds

Considerable attention has been paid to marine derived endophytic fungi, owing to their capacity to produce novel secondary metabolites with potent bioactivities. In this study, two new compounds with a prenylated diphenyl ether structure—diorcinol L (1) and (R)-diorcinol B (2)—were isolated from the marine algal-derived endophytic fungus Aspergillus tennesseensis, along with seven known compounds: (S)-diorcinol B (3), 9-acetyldiorcinol B (4), diorcinol C (5), diorcinol D (6), diorcinol E (7), diorcinol J (8), and a dihydrobenzofuran derivative 9. Their structures were elucidated by extensive NMR spectroscopy studies. Compound 2 represents the first example of an R-configuration in the prenylated moiety. All these isolated compounds were examined for antimicrobial and cytotoxic activities. Compounds 1–9 exhibited antimicrobial activities against some human- and plant-pathogenic microbes with MIC values ranging from 2 to 64 μg/mL. Moreover, compound 9 displayed considerable inhibitory activity against the THP-1 cell line in vitro, with an IC50 value of 7.0 μg/mL.

scholarly journals Anti-Food Allergic Compounds from Penicillium griseofulvum MCCC 3A00225, a Deep-Sea-Derived Fungus

Marine Drugs ◽  
2021 ◽  
Vol 19 (4) ◽  
pp. 224
Author(s):  
Cui-Ping Xing ◽  
Dan Chen ◽  
Chun-Lan Xie ◽  
Qingmei Liu ◽  
Tian-Hua Zhong ◽  
...  
Keyword(s):  
Deep Sea ◽  
Spectroscopic Data ◽  
Positive Control ◽  
X Ray ◽  
X Ray Crystallography ◽  
Ic50 Value ◽  
Penicillium Griseofulvum ◽  
New Compounds ◽  
Basophilic Leukemia

Ten new (1–10) and 26 known (11–36) compounds were isolated from Penicillium griseofulvum MCCC 3A00225, a deep sea-derived fungus. The structures of the new compounds were determined by detailed analysis of the NMR and HRESIMS spectroscopic data. The absolute configurations were established by X-ray crystallography, Marfey’s method, and the ICD method. All isolates were tested for in vitro anti-food allergic bioactivities in immunoglobulin (Ig) E-mediated rat basophilic leukemia (RBL)-2H3 cells. Compound 13 significantly decreased the degranulation release with an IC50 value of 60.3 μM, compared to that of 91.6 μM of the positive control, loratadine.

scholarly journals Two new compounds from leaves of Bruguiera cylindrica (L.) Blume with the in vitro α-glucosidase inhibitory activity

2021 ◽  
Vol 23 (4) ◽  
Author(s):  
Thuy Thi Le Nguyen ◽  
Tung Thanh Bui ◽  
Phung Kim Phi Nguyen ◽  
Chi Minh Tran ◽  
Tu Dang Cam Phan ◽  
...  
Keyword(s):  
Inhibitory Activity ◽  
Ethyl Acetate Extract ◽  
Chemical Constituents ◽  
Positive Control ◽  
Chemical Structures ◽  
Ic50 Values ◽  
Bruguiera Cylindrica ◽  
New Compounds ◽  
Better Than

Introduction: Bruguiera cylindrica is one of the mangrove plants belonging to Bruguiera genus. This genus is characterized by the presence of a large number of compounds, but the research on bioactivities has not been investigated so far. In the present research, the α-glucosidase inhibitory activity, as well as chemical constituents of the ethyl acetate extract of this plant, were studied. Methods: The chemical structures of two new compounds were elucidated by spectroscopic and computational methods. Results: Two new compounds, benzobrugierol (1) and bruguierine (2), were isolated from leaves of Bruguiera cylindrica (L.) Blume, together with nine known ones, including lupeol (3), betulin (4), chrysoeriol (5), glut-5-ene-3-ol (6), cholesta-4-ene-3-one (7), 3α-(Z)-coumaroyllupeol (8), 3α-(E)-coumaroyllupeol (9), 3β-hydroxycholesta-5-ene-7-one (10) and β-sitosterol 3-O-β-D-glucopyranoside (11). Extracts and some isolated compounds were evaluated for α-glucosidase inhibitory activities. Conclusion: The results showed that most of the extracts and tested compounds exhibited activities better than the positive control acarbose, especially two new compounds 1 and 2 with their IC50 values of 17.9 ± 0.4 and 34.6 ± 0.7 (mg/mL), respectively.

Sign in / Sign up

Export Citation Format

Share Document