Theoretical design of novel antimalarial agents against P. falciparum strain, Dd2 through the QSAR modeling of synthesized 2′-substituted triclosan derivatives

Background:Malaria, caused by the deadly Plasmodium falciparum strain, claims the lives of millions of people annually. The emergence of drug-resistant strains of P. falciparum to the artemisinin-based combination therapy (ACT), the last line of defense against malaria, is worrisome and urges for the development of new chemo-types with a new mode of action. In the search of new antimalarial agents, hybrids of triazoles and other known antimalarial drugs have been reported to possess better activity than either of the parent compounds administered individually. Despite their better activity, no hybrid antimalarial drugs have been developed so far.Objective:In the hope of developing new antimalarial prototypes, we propose the design, synthesis and antimalarial evaluation of novel sulfoximine-triazole hybrids owing to their interesting biological and physiological properties.Methods:The sulfoximine part of the hybrid will be synthesized via imidation of the corresponding sulfoxide. Propargylation of the NH moiety of the sulfoximine followed by copper-catalyzed click chemistry with benzyl azide was envisaged to provide the target sulfoximine-triazole hybrids.Results:Five novel sulfoximine-triazole hybrids possessing various substituents on the sulfoximine moiety have been successfully synthesized and evaluated for their antiplasmodial and cytotoxicity activities. The results revealed that the co-presence of the sulfoximine and triazole moieties along with a lipophilic alkyl substituent on the sulfur atom impart significant activity.Conclusion:Sulfoximine-triazole hybrids could be used as a prototype for the synthesis of new derivatives with better antiplasmodial activities.

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A QSAR Modeling on Aurone Derivatives as Antimalarial Agents

Asian Journal of Chemistry ◽

10.14233/ajchem.2020.22846 ◽

2020 ◽

Vol 32 (11) ◽

pp. 2839-2845

Author(s):

R. Hadanau

Keyword(s):

Qsar Model ◽

Quantitative Structure Activity Relationship ◽

Multilinear Regression ◽

Qsar Modeling ◽

Qsar Analysis ◽

Antimalarial Agents ◽

Inhibition Concentration ◽

Qsar Models ◽

Semi Empirical ◽

Statistical Criteria

A quantitative structure activity relationship (QSAR) analysis was performed on several compound and aurone derivatives (1-16) and 17-21 compounds were used as internal and external tests, respectively. Studies have investigated aurone derivatives; however, for aurone compounds, QSAR analysis has not been conducted. The semi-empirical PM3 method of HyperChem for Windows 8.0 was used to optimise the aurone derivative structures to acquire descriptors. For 15 influential descriptors, the multilinear regression MLR analysis was conducted by employing the backward method, and four new QSAR models were obtained. According to statistical criteria, model 2 was the optimum QSAR model for predicting the inhibition concentration (IC50) theoretical value against novel aurone derivatives. The modelling of 40 (22-61) aurone compounds was achieved. Six novel compounds (54, 55, 58, 59, 60, and 61) were synthesized in a laboratory because the IC50 of these compounds was lower than that of chloroquine (IC50 = 0.14 μM).

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QSAR Modeling of Bisbenzofuran Compounds using 2D-Descriptors as Antimalarial Agents

International Journal of Trend in Scientific Research and Development ◽

10.31142/ijtsrd9497 ◽

2018 ◽

Vol Volume-2 (Issue-2) ◽

pp. 769-783

Author(s):

Tripti Kaushal ◽

Anita K ◽

Bashirulla Shaik | Vijay K. Agrawal ◽

Keyword(s):

Qsar Modeling ◽

Antimalarial Agents

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Antioxidant and Antimalarial Activities of Phenolic Compounds from Leaves of Macaranga beccariana Merr.

JURNAL KIMIA MULAWARMAN ◽

10.30872/jkm.v15i2.611 ◽

2018 ◽

Vol 15 (2) ◽

pp. 106

Author(s):

Eva Marliana ◽

Chairul Saleh ◽

Medi Hendra

Keyword(s):

Antioxidant Activity ◽

Structure Elucidation ◽

Methanol Extract ◽

Antimalarial Activity ◽

Endemic Plant ◽

1H And 13C Nmr ◽

Antimalarial Agents ◽

Falciparum Strain ◽

Positive Controls

Macaranga beccariana Merr. is an endemic plant of Kalimantan which is no report yet about its biological activity and isolated compounds. Therefore, in order to know the potency of M. beccariana, determination of antioxidant and antimalarial activities along with isolation of bioactive compounds from this plant must be carried out. In this research, the leaves of M. beccariana was extracted using methanol to obtain methanol extract. Furthermore, the extract was separated and purified to obtain compound 1 and compound 2. Based on structure elucidation using spectrometer analysis including UV, 1H and 13C NMR, compounds 1 and 2 which belong to phenolics were identified as 4-hidroxybenzoic acid and 3,4-dihidroxybenzoic acid, respectively. Moreover, antioxidant activity using DPPH (2,2-diphenyl-1-picrylhydrazyl) and antimalarial activity towards Plasmodium falciparum strain 3D7 using Giemsa staining were performed. Rutine and chloroquine difosfat were used as positive controls for antioxidant and antimalarial, respectively. The results showed that the methanol extract of M. beccariana and its isolated compounds (1 and 2) are active for those activities. It can be concluded that the leaves of M. beccariana has good potency as antioxidant and antimalarial agents.

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