A novel non-stochastic quadratic fingerprints-based approach for the ‘in silico’ discovery of new antitrypanosomal compounds

Montero-Torres, Alina; Gómez, María Celeste Vega; Marrero-Ponce, Yovani; Rolón, Míriam; Gómez‐Barrio, Alicia; Escario, José Antonio; Arán, Vicente J.; Martínez-Fernández, A. R.; Meneses‐Marcel, Alfredo

doi:10.1016/j.bmc.2005.06.049

Cited by 49 publications

(13 citation statements)

References 41 publications

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“…In this sense, it was successfully applied to the virtual (computational) screening of novel anthelmintic compounds, which were then synthesized and in vivo evaluated on Fasciola hepatica [17]. Studies for the fast-track discovery of novel antibacterial [18], paramphistomicide [15], antimalarial [16,19], trichomonicidal [20], and tripanocidals [21] lead-like chemicals were also conducted with this theoretical approach. In addition, the atom-based quadratic indices have been extended to consider three-dimensional features of small/medium-sized molecules based on the trigonometric-3D-chiralitycorrection factor approach [22,23].…”

Section: Introductionmentioning

confidence: 99%

Bond-based global and local (bond, group and bond-type) quadratic indices and their applications to computer-aided molecular design. 1. QSPR studies of diverse sets of organic chemicals

Marrero-Ponce

Torrens

Alvarado

et al. 2006

J Comput Aided Mol Des

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The concept of atom-based quadratic indices is extended to a series of molecular descriptors (MDs) (both total and local) based on adjacency between edges. The kth edge-adjacency matrix (E ( k )) denotes the matrix of bond-based quadratic indices (non-stochastic) with respect to the canonical basis set. The kth "stochastic" edge-adjacency matrix, ES ( k ), is here proposed as a new molecular representation easily calculated from E ( k ). Then, the kth stochastic bond-based quadratic indices are calculated using ES ( k ) as operators of quadratic transformations. The study of six representative physicochemical properties of octane isomers was used to compare the ability of both series of MDs to produce significant quantitative structure-property relationship (QSPR) models. Moreover, the general performance of the new MDs in this QSPR study has been evaluated with respect to other 2D/3D well-known sets of indices and the obtained results shown a quite satisfactory behavior of the present method. The novel bond-level MDs were also used for the description and prediction of the boiling point of 28 alkyl-alcohols and to the modeling of the specific rate constant (log k) of 34 derivatives of 2-furylethylenes. These models were statistically significant and showed very good stability to data variation in leave-one-out (LOO) cross-validation experiment. The comparison with other approaches (edge- and vertices-based connectivity indices, total and local spectral moments, and quantum chemical descriptors as well as E-state/biomolecular encounter parameters) expose a good behavior of our method in this QSPR studies. The approach described in this report appears to be a very promising structural invariant, useful for QSPR/QSAR studies, similarity/diversity analysis, and computer-aided "rational" molecular (drug) design.

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Section: Introductionmentioning

confidence: 99%

Bond-based global and local (bond, group and bond-type) quadratic indices and their applications to computer-aided molecular design. 1. QSPR studies of diverse sets of organic chemicals

Marrero-Ponce

Torrens

Alvarado

et al. 2006

J Comput Aided Mol Des

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“…At the end of 48 h, >70 per cent of the cells showed loss of flagellum, granulation, and round morphology with substantial reduction in size as compared to control promastigotes, suggesting cytoplasmic condensation and shrinkage, established marker of apoptosis25, which may be the possible cause of cell death, an effect exerted by plumericin. This compound caused a reduction in the macrophage infection and its effect on infected macrophages should be of great interest, since the radical group orientation influences the anti-parasitic activity of some compounds26. The strong activity of the tetracyclic iridoid plumericin can be explained by the presence of an α-methylene γ-lactone moiety, susceptible to undergo a Michael-type addition with biological nucleophiles27.…”

Section: Discussionmentioning

confidence: 99%

Antiparasitic activity of plumericin & isoplumericin isolated from Plumeria bicolor against Leishmania donovani

Sharma¹,

Singh²,

Kumar³

et al. 2011

Indian Journal of Medical Research

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Background & objectives:The severe toxicity, exorbitant cost and emerging resistance of Leishmania species against most of the currently used drugs underscores the urgent need for the alternative drugs. The present study evaluates in vitro anti-leishmanial activity of Plumeria bicolor and its isolated compounds.Methods:The in vitro anti-parasitic activity of chloroform extract of Plumeria bicolor, plumericin and isoplumericin were tested alongwith appropriate controls against promastigote and amastigote forms of Leishmania donovani using 96 well microtiter plate. The concentration used for assessing the anti-leishmanial activity of extract of Plumeria bicolor and both isolated compounds were 100 μg/ml and 15 μM, respectively. The viability of the cells was assessed by MTT assay. The cytotoxicity of these compounds was performed against J774G8 murine macrophage cells lines at the concentration of 30 μM.Results:The Plumeria bicolor extract showed activity with the IC50 of 21±2.2 and 14±1.6 μg/ml against promastigote and amastigote forms of L. donovani, respectively. Plumericin consistently showed high activity with the IC50 of 3.17±0.12 and 1.41±0.03 μM whereas isoplumericin showed the IC50 of 7.2±0.08 μM and 4.1±0.02 μM against promastigote and amastigote forms, respectively. Cytotoxic effect of the chloroform extract of P. bicolor, plumericin and isoplumericin was evaluated in murine macrophage (J774G8) model with CC50 value of 75±5.3 μg/ml, 20.6±0.5 and 24±0.7 μM, respectively.Interpretation & conclusions:Our results indicated that plumericin showed more potent activity than isoplumericin and might be a promising anti-leishmanial agent against L. donovani.

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“…Plumericin caused a reduction of the macrophage infection similar to Amphotericin B, the drug used more frequently when patients do not respond to antimonials, the first line chemotherapy (IC 50 of 0.9 M for plumericin and of 1 M for Amphotericin B). This difference between the effects of the two isomers on infected macrophages should be of great interest, since the radical group orientation influences the antiparasitic activity of some compounds (Montero-Torres et al, 2005). As far as we know this is the first time that antileishmanial activity is demonstrated for these types of iridoids.…”

Section: Cell Cytotoxicity Bioassaysmentioning

confidence: 90%

Spirolactone iridoids might be responsible for the antileishmanial activity of a Peruvian traditional remedy made with Himatanthus sucuuba (Apocynaceae)

Castillo¹,

Arévalo²,

Herrera³

et al. 2007

Journal of Ethnopharmacology

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Extracts of seven medicinal plants used specifically against cutaneous leishmaniasis in the Madre de Dios region of Peru were evaluated in vitro against promastigote and axenic amastigote forms of Leishmania amazonensis. One of them showed interesting leishmanicidal activities (IC 50 = 5 g/ml in amastigotes). Bio-guided isolation of the stem bark's ethanol extract of Himatanthus sucuuba (Spruce ex Müll. Arg.) Woodson (Apocynaceae) afforded the spirolactone iridoids isoplumericin and plumericin. The latter showed a reduction of macrophage infection similar to that of the reference drug Amphotericin B (IC 50 = 0.9 and 1 M, respectively). These findings validate the traditional use of Himatanthus sucuuba in the treatment of cutaneous leishmaniasis (Uta) in Peru.

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A novel non-stochastic quadratic fingerprints-based approach for the ‘in silico’ discovery of new antitrypanosomal compounds

Cited by 49 publications

References 41 publications

Bond-based global and local (bond, group and bond-type) quadratic indices and their applications to computer-aided molecular design. 1. QSPR studies of diverse sets of organic chemicals

Bond-based global and local (bond, group and bond-type) quadratic indices and their applications to computer-aided molecular design. 1. QSPR studies of diverse sets of organic chemicals

Antiparasitic activity of plumericin & isoplumericin isolated from Plumeria bicolor against Leishmania donovani

Spirolactone iridoids might be responsible for the antileishmanial activity of a Peruvian traditional remedy made with Himatanthus sucuuba (Apocynaceae)

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