Rational drug design

Mandal, Soma; Moudgil, Meenal; Mandal, Saptarshi

doi:10.1016/j.ejphar.2009.06.065

Cited by 239 publications

(130 citation statements)

References 39 publications

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“…These hybrids, obtained by synthetic pathways reported in recent scientific literature, correspond to the previous virtual screening performed using the OSIRIS and Molinspiration platforms. [23][24][25][26][27] The obtained results evidence the potential in further biological studies of these derivatives thanks to their considerable drug-score and excellent reaction yields.…”

Section: Resultsmentioning

confidence: 94%

“…23,24 Lipinki's rule of five parameters were calculated using the Molinspiration virtual platform (http://www.molinspiration.com/services/). The toxicity risk profile evaluation was accomplished employing the OSIRIS program available free at http://www.organicchemistry.org/prog/peo.…”

Section: Methodsmentioning

confidence: 99%

“…In the Molinspiration program, the occurrence frequency of each fragment is determined within the collection created by shreddering 3300 traded drugs, as well as 15000 commercially available chemicals yielding a complete list of all available fragments. 23 In this work, the Molinspiration program was used for the fragment based drug-likeness calculation of all desired compounds (Table 1). TPSA has been shown to be a very good descriptor characterizing drug absorption, including intestinal absorption, bioavailability, Caco-2 permeability and blood-brain barrier penetration.…”

Section: Rational Molecular Designmentioning

confidence: 99%

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Property-based design and synthesis of new chloroquine hybrids via simple incorporation of 2-imino-thiazolidin-4-one or 1h-pyrrol-2, 5-dione fragments on the 4-amino-7-chloroquinoline side chain

Rojas¹,

Kouznetsov²

2011

J. Braz. Chem. Soc.

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No presente trabalho realizou-se a síntese de novos N-derivados da 4-amino-7-cloroquinolina modificando seletivamente o grupo amino terminal das N- (7-cloroquinolin-4-il)-alquildiaminas, a base do fármaco cloroquina (CQ) mediante a incorporação de sistemas heterocíclicos da 2-imino-tiazolidin-4-ona e 1H-pirrol-2,5-diona. Esses derivados foram selecionados graças às suas propriedades características, e avaliados mediante crivado virtual empregando as plataformas OSIRIS e Molinspiration. Os derivados quinolínicos assim desenhados e sintetizados poderiam incrementar a atividade antimalárica dos análogos da CQ sem afetar a lipofilia como tem se descrito na literatura, postulando-se como candidatos em posteriores testes biológicos.In the present work, the syntheses of new 4-amino-7-chloroquinoline N-derivatives were performed by selective modification of the side chain amino group of N- (7-chloroquinolin-4-yl) alkyldiamines, basis framework of chloroquine (CQ) drug through the incorporation of heterocyclic 2-imino-thiazolidin-4-one and 1H-pyrrol-2,5-dione systems. These potential activity modulators were selected thanks to their characteristic properties, and evaluated by virtual screening employing the OSIRIS and Molinspirations platforms. Designed and synthesized quinolinic derivatives could increase the antimalarial activity of CQ analogues without affecting the lipophilicity as described in literature, suggesting them as candidates for further biological assessments.

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Section: Resultsmentioning

confidence: 94%

Section: Methodsmentioning

confidence: 99%

Section: Rational Molecular Designmentioning

confidence: 99%

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Property-based design and synthesis of new chloroquine hybrids via simple incorporation of 2-imino-thiazolidin-4-one or 1h-pyrrol-2, 5-dione fragments on the 4-amino-7-chloroquinoline side chain

Rojas¹,

Kouznetsov²

2011

J. Braz. Chem. Soc.

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“… Evaluation of in-vivo experiments, bioinformatics analysis, etc.  Preclinical evaluation 30,31,32 .…”

Section: Fig 4: Approach Of Drug Design With Unknown Targetmentioning

confidence: 99%

Untitled

2018

IJPSR

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ABSTRACT:The process of drug development and drug discovery is very challenging, expensive and time consuming. It has been accelerated due to development of computational tools and methods. Over the last few years, computer aided drug design (CADD) also known as in silico screening has become a powerful technique because of its utility in various phases of drug discovery and development through various advanced features. In silico screening also paves path for the synthesis and screening of selected compounds for better therapeutics. This review focuses on computational chemistry and computer aided drug discovery which are aimed to cover a wide range of computational approaches including new methodologies as well as practical aspects in this area. This review provides an insight about the developmental chain, approaches and applications of CADD; various data sources; computational methods for the discovery of new molecular entities; clinically approved drugs developed through CADD; and also summarizes the crucial steps of in silico drug designing like homology modelling, docking, multi-target searching and design, pharmacophore development, conformation generation and quantitative structure activity relationship (QSAR).

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“…The most active compounds designing so far-3-(3,4-difluorophenyl)-coumarin-7-O-sulfamate (4) The described above process of development of new steroid sulfatase inhibitors is expensive, time consuming, and requires collaboration of experts from different disciplines, such as: biology, chemistry, biochemistry, pharmacology, etc. However, according to recently recommended ideas in designing new drugs [11], this challenging process could be supported by a computational chemistry [12,13]. The computer-aided drug design (CADD) is a valuable and promising tool [14], especially in the contexts of the rational drug discovery.…”

Section: Introductionmentioning

confidence: 99%

Geometry optimization of steroid sulfatase inhibitors - the influence on the free binding energy with STS

et al. 2017

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In the paper we review the application of two techniques (molecular mechanics and quantum mechanics) to study the influence of geometry optimization of the steroid sulfatase inhibitors on the values of descriptors coded their chemical structure and their free binding energy with the STS protein. We selected 22 STS-inhibitors and compared their structures optimized with MM+, PM7 and DFT B3LYP/6-31++G* approaches considering separately the bond lengths, angles, dihedral angles and total energies. We proved that different minimum energy conformers could be generated depending on the choice of the optimization method. However, the results indicated that selection of the geometry optimization method did not affect the optimal STS inhibitor coordinates, and hence the values of molecular descriptors which describe the 3D structure of the molecule. To study the interaction pattern of the STS inhibitors (optimized using different methods) with the target receptor we applied two strategies: AutoDock and PathDock. The docking studies point out that selection of software to docking simulation is one of the crucial factors determining the binding mode of STS inhibitors with their molecular target. Other factor is related to the ligand orientation in the binding pocket. Finally, obtained results indicate that MM+ and PM7 methods (faster and less expensive) could be successfully employed to geometry optimization of the STS inhibitors before their docking procedure as well as for molecular descriptors calculations.

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Rational drug design

Cited by 239 publications

References 39 publications

Property-based design and synthesis of new chloroquine hybrids via simple incorporation of 2-imino-thiazolidin-4-one or 1h-pyrrol-2, 5-dione fragments on the 4-amino-7-chloroquinoline side chain

Property-based design and synthesis of new chloroquine hybrids via simple incorporation of 2-imino-thiazolidin-4-one or 1h-pyrrol-2, 5-dione fragments on the 4-amino-7-chloroquinoline side chain

Untitled

Geometry optimization of steroid sulfatase inhibitors - the influence on the free binding energy with STS

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