Computational modeling studies on anti-HIV-1 non-nucleoside reverse transcriptase inhibition by dihydroalkoxybenzyloxopyrimidines analogues: an electrotopological atomistic approach

Sapre, Nitin S.; Bhati, Tarang; Gupta, Swagata; Pancholi, Nilanjana; Raghuvanshi, Urmila; Dubey, Divya; Rajopadhyay, Vandana; Sapre, Neelima

doi:10.4236/jbpc.2011.23041

Cited by 2 publications

(4 citation statements)

References 50 publications

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“…2,4-Dichloroacetophenone was reacted with aromatic and heterocyclic aldehydes in ethanolic sodium hydroxide solution to produce 3-(substituted)-1-(2,4-dichloro-phenyl)-propen-1-ones (1a-c) as starting materials. Compound 1a was reacted with hydrogen peroxide in alkaline medium to give (2,4dichlorophenyl)-3-(4-methoxyphenyl)oxiran-2-yl)methanone (2), which was condensed with thiourea in alcoholic potassium hydroxide to afford the corresponding thioxo-pyrimidinone (3). When compound 3 was reacted with 2,3,4,6-tetra-O-acetyl-α-D-glucopyranosyl bromide or alkyl chloride in alkaline medium gave the corresponding 4-(4-methoxy-phenyl)-6-(2,4-dichlorophenyl)-1,3-di-(2,3,4,6-tetra-O-acetyl-β-D-glucopyranosyl)-2-thioxotetra-hydro-pyrimidin -5-one (4) and compounds 5a,b, respectively (Scheme 1).…”

Section: Resultsmentioning

confidence: 99%

“…agents (2,3) , anticancer (4,5) , antiviral (6,7) , antimicrobial (8)(9)(10)(11) , anti-inflammatory (12,13) and potential antitubercular agents (14) . Thiazolopyrimidine has good antiinflammatory, analgestic anticonvulsant and antiparkinsonian (15) , anticancer (16) , and binding affinity to the CRH-R1 receptor, thus showing promise as a new class of potential anxiolytics and/or antidepressants (17) .…”

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Synthesis, Molecular Docking and Biological Evaluation of Some Novel Heterocyclic Derivatives

2012

Egypt. J. Chem.

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SERIES of heterocyclic derivatives 2-15 including pyrimidinone ……and pyrimidine thione rings were synthesized by using chalcones 1a-c as starting materials. Treatment of compound 1a with hydrogen peroxide afforded the corresponding epoxide 2, which afford thioxopyrimidine derivative 3 upon the reaction with thiourea. The latter compound was treated with halo-derivatives to give the corresponding N-substituted thioxopyrimidine derivatives 4 and 5. Moreover, compounds 6-10 were prepared by the treatment of compound 1b with acetyl acetone, hydrazine hydrate, urea, thiourea or thiosemicarbazide, respectively. Also, compound 10 was condensed with p-chlorobenzaldehyde and chloroethanol to give 11 and 12, respectively. The alkylation of 9a with methyl iodide or ethylchloroacetate accessing the S-substituted pyrimidine derivatives 13 and 14, respectively was carried out. Also, compound 9a was reacted with p-methoxybenzaldehyde and bromoacetic acid to afford the corresponding thiazolopyrimidine 15. Characterization and structural elucidation of the products was realized based on chemical and spectral analyses. Furthermore, a molecular docking study was performed in order to predict the anticancer activity of these compounds against Tyrosine Kinase enzyme hoping to find any promising affinity that could be of potential anticancer activity. Also, the biological evaluation of some prepared compounds has been assessed and some of them revealed promising antioxidant activity.

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Section: Resultsmentioning

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Synthesis, Molecular Docking and Biological Evaluation of Some Novel Heterocyclic Derivatives

2012

Egypt. J. Chem.

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“…35 Efforts are ongoing to make structural changes so that the DABO analogs demonstrate enhanced potency. [43][44][45][46] The 3-dimensional RT complex-DABO crystal structure analysis has provided newer dimensions to interpretation of the drug-receptor interaction prole, and this has certainly aided in substantiating the SAR analyses for enhanced structural renement. [36][37][38][39][40][41][42] The common structure of DABO consists of a pyrimidinone ring and a di-uoro substituted aromatic ring attached through a substituted CH bridging group.…”

Section: Introductionmentioning

confidence: 99%

“…Earlier studies on DABO are based on various SAR analyses, where the structural requirements for enhancing the biological activity have been quantitatively analyzed. [43][44][45][46] The 3-dimensional RT complex-DABO crystal structure analysis has provided newer dimensions to interpretation of the drug-receptor interaction prole, and this has certainly aided in substantiating the SAR analyses for enhanced structural renement. [47][48][49][50][51][52] The present study deals with design of novel NNRTIs by performing chemometric analyses of two important types of descriptors namely (a) 3D pharmacophoric [dipole moment, S ALL , HD ALL , R ALL and HA ALL ] and (b) 2D average alignment [octanol-water partition coefficient (C log P) descriptors in understanding the interactions potential of 5-alkyl-2-alkylamino-6-(2,6-diuorophenylalkyl)-3,4-dihydropyrimidin-4(3H)-one (DABO) analogs in the NNIBP.…”

Section: Introductionmentioning

confidence: 99%

In silico de novo design of novel NNRTIs: a bio-molecular modelling approach

Jain¹,

Gupta

Sapre³

et al. 2015

RSC Adv.

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Six novel non-nucleoside reverse transcriptase inhibitors exhibiting high efficacy are designed using in silico mathematical modelling techniques and the results are validated using a docking technique. An in silico assessment of interaction potential and structural requirements of 5-alkyl-2-alkylamino-6-(2,6difluorophenylalkyl)-3,4-dihydropyrimidin-4(3H)-one (DABO) analogues in the non-nucleoside inhibitor binding pocket is also performed. Efficient use of 3D-pharamacophoric (S ALL , HD ALL , HA ALL and R ALL ) and 3D-averaged alignment (C log P and dipole moment) descriptors is made in this study. The chemometric analyses, using support vector machine, back propagation neural network and multiple linear regression, are performed. The relative potentials of these chemometric methods is also assessed and the results,indicates that SVM describes the relationship between the descriptors and inhibitory activity in a better manner. The results also suggest that there is a non-linear relationship between the descriptors and inhibitory activity. The study further suggests that isopropyl/propenyl groups as R and R 0 , oxobutyl group as X and di or tri-substitution as R 00 are the best suited substituents for exhibiting better inhibitory activity.View Article Online a pEC 50 ¼ Àlog EC 50 (where EC 50 is the effective concentration of a compound required to activate 50% protection of MT-4 cell against the cytopathic effect of HIV-1). The data points a represent the test set and b as Outliers.This journal is

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Computational modeling studies on anti-HIV-1 non-nucleoside reverse transcriptase inhibition by dihydroalkoxybenzyloxopyrimidines analogues: an electrotopological atomistic approach

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Cited by 2 publications

References 50 publications

Synthesis, Molecular Docking and Biological Evaluation of Some Novel Heterocyclic Derivatives

Synthesis, Molecular Docking and Biological Evaluation of Some Novel Heterocyclic Derivatives

In silico de novo design of novel NNRTIs: a bio-molecular modelling approach

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