Appraisal of Bioactive Compounds of Betel Fruit as Antimalarial Agents by Targeting Plasmepsin 1 and 2: A Computational Approach

In many countries, the fruit of betel (Piper betle Linn) is traditionally used as medicine for treating malaria. It is a fatal disease, and existing medications are rapidly losing potency, necessitating the development of innovative pharmaceutics. The current study attempted to determine the compounds in the n-hexane fraction of betel fruit extract and investigate the potential inhibition of bioactive compounds against aspartic protease plasmepsin 1 (PDB ID: 3QS1) and plasmepsin 2 (PDB ID: 1LEE) of Plasmodium falciparum using a computational approach. The ethanol extract was fractionated into n-hexane and further analyzed using gas chromatography-mass spectrometry (GC-MS) to obtain information regarding the compounds contained in betel fruit. Each compound’s potential antimalarial activity was evaluated using AutoDock Vina and compared to artemisinin, an antimalarial drug. Molecular dynamics simulations (MDSs) were performed to evaluate the stability of the interaction between the ligand and receptors. Results detected 20 probable compounds in the n-hexane extract of betel fruit based on GC-MS analysis. The docking study revealed that androstan-17-one,3-ethyl-3-hydroxy-, (5 alpha)- has the highest binding affinity for plasmepsin 1 and plasmepsin 2. The compound exhibits a similar interaction with artemisinin at the active site of the receptors. The compound does not violate Lipinski’s rules of five. It belongs to class 5 toxicity with an LD50 of 3000 mg/kg. MDS results showed stable interactions between the compound and the receptors. Our study concluded that androstan-17-one,3-ethyl-3-hydroxy-, (5 alpha)- from betel fruit has the potential to be further investigated as a potential inhibitor of the aspartic protease plasmepsin 1 and plasmepsin 2 of Plasmodium falciparum.

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Preliminary phytochemical screening, antimicrobial potentials and GC-MS analysis of Secamone afzelli Rhoem (Asclepiadaceae) leaves extracts

Nigerian Journal of Pure and Applied Sciences ◽

10.48198/njpas/20.a10 ◽

2020 ◽

pp. 3728-3738

Author(s):

Oladapo E. Oyinloye ◽

Olumuyiwa. S. Alabi

Keyword(s):

Ethyl Acetate ◽

Bioactive Compounds ◽

Ethanol Extract ◽

Inhibition Zone ◽

Gas Chromatography Mass Spectrometry ◽

Ms Analysis ◽

Soxhlet Apparatus ◽

Ethanol Extracts ◽

Tract Infections ◽

Gastro Intestinal Tract

Secamone afzelli is used ethno-medicinally as remedies for stomach, colic and gastro-intestinal tract infections. This study screened the hexane, ethyl acetate and ethanol extracts of S. afzelli leaves for phytocompounds, antimicrobial activity and identified bioactive compounds in the most active extract using Gas Chromatography Mass Spectrometry (GC-MS) analysis. S. afzelli (200mg) leave was extracted by soxhlet apparatus using three solvents (hexane, ethyl acetate and ethanol) and the phytochemicals determined. Antimicrobial susceptibility and minimum inhibitory concentrations (MICs) was determined by agar-diffusion and agar-dilution methods respectively against selected resistant bacterial and fungal clinical isolates. The most active of the three crude extracts was analysed by GC-MS for bioactive compounds identification. Presence of carbohydrates, anthraquinone, glycosides, proteins, tannin, phenolic compounds and steroids were determined. The three extracts (hexane, ethyl acetate, and ethanol extracts) had antibacterial (Range of inhibition zone = 10 to 18 mm and MICs 12.5 to 200 mg/mL) but no antifungal activity. The ethanol extract was the most active with 29 bioactive compounds including piperazine, phytol, leucine methyl ester, N-methyl-N-(1-methylethyl)- 1Pentanamine, 7-propyl-pyrrolizin-1-thione and 4,5-dimethylnonane. The antibacterial activity and arrays of bioactive compounds detected in S. afzelli leaves suggest that the plant may be a good source of novel antimicrobial compounds.

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Various Parts of Helianthus annuus Plants as New Sources of Antimalarial Drugs

Evidence-based Complementary and Alternative Medicine ◽

10.1155/2019/7390385 ◽

2019 ◽

Vol 2019 ◽

pp. 1-7

Author(s):

Wiwied Ekasari ◽

Dwi Widya Pratiwi ◽

Zelmira Amanda ◽

Suciati ◽

Aty Widyawaruyanti ◽

...

Keyword(s):

Plasmodium Falciparum ◽

Helianthus Annuus ◽

Antimalarial Activity ◽

Ethanol Extract ◽

The Other ◽

Antimalarial Agent ◽

A Value ◽

Ethanol Extracts

Background. Each part of H. annuus plants is traditionally used as medicinal remedies for several diseases, including malaria. Antimalarial activity of the leaf and the seed has already been observed; however, there is no report about antimalarial activity of the other parts of H. annuus plants. In this study, we assess in vitro and in vivo antimalarial activity of each part of the plants and its mechanism as antimalarial agent against inhibition of heme detoxification. Objective. To investigate the antimalarial activity of various parts of H. annuus. Methods. Various parts of the H. annuus plant were tested for in vitro antimalarial activity against Plasmodium falciparum 3D7 strain (chloroquine-sensitive), in vivo antimalarial activity against P. berghei using Peters’ 4-day suppressive test in BALB/c mice, curative and prophylaxis assay, and inhibition of heme detoxification by evaluating β-hematin level. Results. Ethanol extract of the roots showed the highest antimalarial activity, followed by ethanol extract of leaves, with IC50 values of 2.3 ± 1.4 and 4.3 ± 2.2 μg/mL, respectively and the percentage inhibition of P. berghei of 63.6 ± 8.0 and 59.3 ± 13.2 at a dose of 100 mg/kg, respectively. Ethanol extract of roots produced an ED50 value of 10.6 ± 0.2 mg/kg in the curative test and showed an inhibition of 79.2% at a dose of 400 mg/kg in the prophylactic assay. In inhibition of heme detoxification assay, root and leaf ethanol extracts yielded a lower IC50 value than positive (chloroquine) control with a value of 0.4 ± 0.0 and 0.5 ± 0.0 mg/mL, respectively. Conclusion. There were promising results of the ethanol extracts of root of H. annuus as a new source for the development of a new plant-based antimalarial agent.

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Aktivitas Antimalaria Ekstrak Kasar Etanol dan Fraksi n-Heksana Rumput Bambu (Lophatherum gracile B.) secara in Vitro

ALCHEMY ◽

10.18860/al.v6i1.6766 ◽

2018 ◽

Vol 6 (1) ◽

pp. 18

Author(s):

Ella Wulandari ◽

Dewi Yuliani ◽

Elok Kamilah Hayati ◽

Roihatul Muti'ah

Keyword(s):

Mass Spectrometry ◽

Plasmodium Falciparum ◽

Liquid Chromatography ◽

Antimalarial Activity ◽

Ethanol Extract ◽

Hexane Fraction ◽

Liquid Chromatography Mass Spectrometry ◽

Mosquito Bite

Malaria is a disease caused by infectious parasite Plasmodium falciparum and can be transmitted through mosquito bite. The aim of this research was to study antimalarial activity in vitro on crude ethanol extract and n-hexane fraction of bamboo grass (Lophatherum gracile B.). Extraction was carried out by ethanol 80% solvent and fractionation was conducted by n-hexane. Determination of antimalarial activity was subjected to P. falciparum strain 3D7. According to phytochemical test, crude ethanol extract contained tannin and terpenoid, whilst n-hexane fraction contained tannin and steroid. The capability of crude ethanol extract and n-hexane fraction to inhibit P. falciparum was represented by IC50 value. The value of both samples respectively was 12.49 and 61.49 µg/mL. Identification based on LC-MS (liquid chromatography-mass spectrometry), n-hexane fraction shown the presence of tannin and steroid compounds. Malaria merupakan penyakit yang disebabkan oleh infeksi parasit Plasmodium falciparum yang dapat ditularkan melalui gigitan nyamuk. Penelitian ini bertujuan untuk mengetahui aktivitas antimalaria secara in vitro pada ekstrak kasar etanol dan fraksi n-heksana rumput bambu (Lophatherum gracile B.). Proses ekstraksi dilakukan dengan pelarut etanol 80% dan fraksinasi dengan n-heksana. Uji aktivitas antimalaria dilakukan pada parasit P. falciparum strain 3D7. Hasil uji fitokimia menunjukkan ekstrak etanol mengandung tanin dan terpenoid, sedangkan fraksi n-heksana mengandung tanin dan steroid. Kemampuan ekstrak etanol dan fraksi n-heksana dalam menghambat parasit P. falciparum menghasilkan nilai IC50 masing-masing sebesar 12,49 dan 61,49 µg/mL. Identifikasi senyawa dengan KC-SM (kromatografi cair-spektrometri massa) pada fraksi n-heksana menunjukkan adanya senyawa tanin dan steroid.

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Evaluation of Bioactive Compounds, in Vitro Antioxidant Activity and Acute Toxicity of Ethanol Extract of Morinda lucida Leaves

Asian Journal of Biochemistry, Genetics and Molecular Biology ◽

10.9734/ajbgmb/2021/v7i230171 ◽

2021 ◽

pp. 32-38

Author(s):

F. M. Idih ◽

O. V. Alagbe ◽

V. D. Sheneni ◽

J. Ebune

Keyword(s):

Antioxidant Activity ◽

Bioactive Compounds ◽

Lethal Dose ◽

Ethanol Extract ◽

Gas Chromatography Mass Spectrometry ◽

Medium Size ◽

Traditional Treatment ◽

In Vitro Antioxidant Activity

Plants are known to contain phytochemicals of pharmacological relevance and as such have been utilized in the treatment and management of various diseases. Morinda lucida, a medium size tropical tree belonging to the rubiaceae family and widely distributed in Africa is one of these plants. It has been reportedly used in the traditional treatment and management of diseases. This study is aimed at identifying compounds with pharmacological relevance in the ethanol extract of Morinda lucida leaves, the antioxidant activity and lethal dose determination of the extract. The leaves of Morinda lucida was extracted with ethanol; phytochemical and bioactive compounds analysis, in vitro antioxidant activity and lethal dose (LD50) determinations were carried out. It was observed in the study that the extract contains alkaloids, quinines, quinones, flavonoids and tannins. The gas chromatography mass spectrometry (GC-MS) identified phenol 2, 4-bis (1,1-dimethylethyl) (2.82%), Stilbenes (12.32%), Phenoxazine (2.60%) and Benz(cd) indol-2(1H)-one, 1-methyl- (2.60%) amongst other compounds in the extract. The in vitro antioxidant activity evaluation of the extract revealed that it possesses a significant antioxidant activity which increased with increasing concentration. The LD50 determination revealed the extract was safe as there was no death recorded even at a dose as high as 5000 mg/kg. This study shows that Morinda lucida possesses enormous pharmacological potentials.

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IDENTIFICATION OF BIOACTIVE COMPOUNDS IN CYMODOCEA SERRULATA-A SEAGRASS BY GAS CHROMATOGRAPHY–MASS SPECTROSCOPY

Asian Journal of Pharmaceutical and Clinical Research ◽

10.22159/ajpcr.2018.v11i9.26744 ◽

2018 ◽

Vol 11 (9) ◽

pp. 317

Author(s):

Pushpabharathi N ◽

Jayalakshmi M ◽

Amudha P ◽

Vanitha V

Keyword(s):

Gas Chromatography ◽

Bioactive Compounds ◽

Acid Methyl Ester ◽

Ethanol Extract ◽

Antioxidant Property ◽

Gas Chromatography Mass Spectrometry ◽

Tetradecanoic Acid ◽

Hexahydrofarnesyl Acetone ◽

Gas Chromatography Mass Spectroscopy ◽

Cymodocea Serrulata

Objective: The objective of this study was to identify the lead phytocompounds present in the ethanol extract of the seagrass Cymodocea serrulata by gas chromatography–mass spectrometry (GCMS).Methods: 1 kg of C. serrulata whole seagrass powder was subjected to extraction on polarity basis using five solvent such as hexane, chloroform, ethyl acetate, ethanol, and water. Since ethanol extract showed a maximum antioxidant property, its phytochemicals were investigated using GCMS technique. The phytocompounds identified through GC were interpreted with mass spectra national institute standard and technology library.Result: The GCMS analysis of ethanol extract of C. serrulata identified peaks of six different compounds they are hexahydrofarnesyl acetone (7.70%), hexadecanoic acid, methyl ester (4.11%), tetradecanoic acid (62.89%), pentadecanoic acid(62.89%), cholesta4, 6dien3ol (5.88%), and stigmasterol (19.42%).Conclusion: The GCMS study of C. serrulata ethanol extract unveils the presence of bioactive compounds that have a pharmacological and nutraceutical values.

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Radicicol Confers Mid-Schizont Arrest by Inhibiting Mitochondrial Replication in Plasmodium falciparum

Antimicrobial Agents and Chemotherapy ◽

10.1128/aac.02519-13 ◽

2014 ◽

Vol 58 (8) ◽

pp. 4341-4352 ◽

Cited By ~ 7

Author(s):

Sureshkumar Chalapareddy ◽

Mrinal Kanti Bhattacharyya ◽

Seema Mishra ◽

Sunanda Bhattacharyya

Keyword(s):

Plasmodium Falciparum ◽

Antimalarial Activity ◽

Docking Study ◽

Dependent Manner ◽

Atpase Domain ◽

Concentration Dependent Manner ◽

Developmental Defects ◽

Content Type ◽

Sublethal Doses ◽

Mitochondrial Replication

ABSTRACTRadicicol, an antifungal antibiotic, was previously identified as a compound having antimalarial activity. However, its mechanism of action inPlasmodium falciparumwas not elucidated. While characterizing its antimalarial function, we observed that radicicol manifested two distinct developmental defects in culturedP. falciparumin a concentration-dependent manner. At a low concentration of radicicol, a significant percentage of drug-treated parasites were arrested at the schizont stage, while at a higher concentration, the parasites were unable to multiply from schizont to ring. Also, the newly formed rings and trophozoites were extremely delayed in development, eventually leading to cell death. We intended to characterize the potential molecular target of radicicol at its sublethal doses. Our results demonstrated that radicicol specifically impaired mitochondrial replication. This decrement was associated with a severalfold increment of the topoisomerase VIB transcript as well as protein in treated cells over that of untreated parasites. Topoisomerase VIB was found to be localized in the organelle fraction. Our docking study revealed that radicicol fits into the Bergerat fold of Pf topoisomerase VIB present in its ATPase domain. Altogether, these data allow us to conclude thatP. falciparumtopoisomerase VIB might be one of the targets of radicicol causing inhibition of mitochondrial replication. Hence, radicicol can be suitably employed to explore the mitochondrial physiology of malaria parasites.

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Molecular Docking and QSAR Study of Chalcone and Pyrimidine Derivatives as Potent Anti-Malarial Agents against Plasmodium falciparum

International Letters of Chemistry Physics and Astronomy ◽

10.18052/www.scipress.com/ilcpa.85.23 ◽

2020 ◽

Vol 85 ◽

pp. 23-34

Author(s):

Dayena J. Christian ◽

Rajesh H. Vekariya ◽

Kinjal D. Patel ◽

Dhanji P. Rajani ◽

Smita D. Rajani ◽

...

Keyword(s):

Plasmodium Falciparum ◽

Molecular Docking ◽

Antimalarial Activity ◽

Docking Study ◽

Quantitative Structure Activity Relationship ◽

Negative Influence ◽

Pyrimidine Derivatives ◽

Molecular Docking Study ◽

Qsar Study ◽

Data Set

A data set of chalcone and pyrimidine derivatives with anti-malarial activity against Plasmodium falciparum was employed in investigating the quantitative structure-activity relationship (QSAR). Molecular docking study was performed for plasmodium falciparum dihydrofolate reductase (PfDHFR-TS). Genetic function approximation (GFA) technique was used to identify the descriptors that have influence on anti-malarial activity. The most influencing molecular descriptors identified include thermodynamics, structural and physical descriptors. Generated model was found to be good based on correlation coefficient, LOF, rm2 and rcv2 values. Nrotb, solubility, polarizibility may have negative influence on antimalarial activity or play an important role in growth inhibition of Plasmodium falciparum. The QSAR models so constructed provide fruitful insights for the future development of anti-malarial agents.

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Aktivitas Penghambatan Ekstrak Etanol Daun Cassia Spectabilis Terhadap Pertumbuhan Plasmodium falciparum dan Plasmodium berghei

JURNAL FARMASI DAN ILMU KEFARMASIAN INDONESIA ◽

10.20473/jfiki.v3i1.4088 ◽

2017 ◽

Vol 3 (1) ◽

pp. 17 ◽

Cited By ~ 1

Author(s):

Wiwied Ekasari ◽

Nindya Tresiana ◽

Suciati Iryani ◽

Tutik Sri Wahyuni ◽

Heny Arwaty

Keyword(s):

Plasmodium Falciparum ◽

Methanol Extract ◽

Antimalarial Activity ◽

Ethanolic Extract ◽

Ethanol Extract ◽

In Vivo Test ◽

Ic50 Value ◽

Cassia Spectabilis

Background: Antimalarial screening against nine species of the genus Cassia showed that the methanol extract of leaves Cassia spectabilis have the highest activity. Since it will be used as a traditional medicine, hence it is needed further studies of antimalarial activity of these plants by choosing a safer solvent, namely ethanol. Objective: In vitro anti-malarial activity against Plasmodium falciparum was conducted using the method of Trager and Jensen. Methods: The serial solution tested were: 100, 10, 1, 0.1 and 0.01 µg/ mL, while the in vivo test was performed based on Peter’s test (The days suppressive test) that using P. berghei (strain ANKA) infected mice. Results: The results showed that ethanolic extract of C. spectabilis leaves has inhibitory activity against P. falciparum with IC50 value of 12.52 µg/ mL and against P. berghei with ED50 value of 131.5 mg/kg body weight. Conclusions: A further study to see the potential of ethanol extract from C. Spectabilis leaves as anti-malaria is warranted.

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Aktivitas Penghambatan Ekstrak Etanol Daun Cassia Spectabilis Terhadap Pertumbuhan Plasmodium falciparum dan Plasmodium berghei

JURNAL FARMASI DAN ILMU KEFARMASIAN INDONESIA ◽

10.20473/jfiki.v3i12016.17-21 ◽

2017 ◽

Vol 3 (1) ◽

pp. 17

Author(s):

Wiwied Ekasari ◽

Nindya Tresiana ◽

Suciati Iryani ◽

Tutik Sri Wahyuni ◽

Heny Arwaty

Keyword(s):

Plasmodium Falciparum ◽

Methanol Extract ◽

Antimalarial Activity ◽

Ethanolic Extract ◽

Ethanol Extract ◽

In Vivo Test ◽

Ic50 Value ◽

Cassia Spectabilis

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Synthesis, Antimalarial Evaluation and SAR Study of Some 1,3,5-Trisubstituted Pyrazoline Derivatives

Letters in Organic Chemistry ◽

10.2174/1570178616666190212145754 ◽

2019 ◽

Vol 16 (10) ◽

pp. 807-817 ◽

Cited By ~ 1

Author(s):

Shilpy Aggarwal ◽

Deepika Paliwal ◽

Dhirender Kaushik ◽

Girish Kumar Gupta ◽

Ajay Kumar

Keyword(s):

Antimalarial Activity ◽

Analysis Data ◽

Docking Study ◽

Maximum Activity ◽

Elemental Analysis Data ◽

Mass Spectral ◽

Structure Activity ◽

Pharmacokinetic Properties ◽

Sar Study

The synthesis of a novel series of 1,3,5-trisubstitiuted pyrazoline was achieved by refluxing chalcone derivative with different heteroaryl hydrazines. The newly synthesized compounds were characterized by 1H NMR, 13CNMR, mass spectral and elemental analysis data. The synthetic series of novel pyrazoline hybrids was screened for in vitro schizont maturation assay against chloroquine sensitive 3D7 strain of Plasmodium falciparum. Most of the compounds showed promising in vitro antimalarial activity against CQ sensitive strain. The preliminary structure-activity relationship study showed that quinoline substituted analog at position N-1 showed maximum activity followed by benzothiazole substitution, while phenyl substitution lowers the antimalarial activity. The observed activity was persistent by the docking study on P. falciparum cystein protease falcipain-2. The pharmacokinetic properties were also studied using ADME prediction.

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