Atom, atom-type and total molecular linear indices as a promising approach for bioorganic and medicinal chemistry: theoretical and experimental assessment of a novel method for virtual screening and rational design of new lead anthelmintic

Marrero-Ponce, Yovani; Castillo-Garit, Juan A.; Olazábal, Ervelio; Serrano, Hector S.; Morales, Alcidez; Castañedo, Nilo; Ibarra-Velarde, Froylán; Huesca-Guillén, Alma; Sánchez, Alicia M.; Torrens, Francisco; Castro, Eduardo A.

doi:10.1016/j.bmc.2004.11.040

Cited by 92 publications

(71 citation statements)

References 37 publications

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“…This ALMA-entropy model present excellent performance in both training and external validation series with Sensitivity (Sn), Specificity (Sp), and Accuracy (Ac) > 80%. Values higher than 75% are acceptable for LDA-QSAR models, according to previous reports [9][10][11][12][13].…”

Section: Introductionsupporting

confidence: 71%

<strong>Multi-target Prediction of Neuroprotective Drugs, Synthesis, Assay, and Theoretical Study of Rasagiline Carbamates</strong>

Durán

Alonso

Caamaño

et al. 2015

Proceedings of MOL2NET, International Conference on Multidisciplinary Sciences

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Abstract:In this work, we developed a multi-target model for neuroprotective compounds reported in the CHEMBL database. The model predicted correctly >8300 experimental outcomes with Accuracy, Specificity, and Sensitivity above 80-90% in training and external validation series. This is model can different outcomes for >30 experimental measures in >400 different experimental protocols and related to >150 molecular and cellular targets present in 11 different organisms (including human). After that, we reported by the first time, the synthesis, characterization, and experimental assays of new series of chiral 1,2-rasagiline carbamate derivatives; not reported in previous works. This work is a synopsis of the results presented in our previous paper: Int

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Section: Introductionsupporting

confidence: 71%

<strong>Multi-target Prediction of Neuroprotective Drugs, Synthesis, Assay, and Theoretical Study of Rasagiline Carbamates</strong>

Durán

Alonso

Caamaño

et al. 2015

Proceedings of MOL2NET, International Conference on Multidisciplinary Sciences

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“…The IR spectra were recorded on a Shimadzu FTIR 8400S spectrophotometer (Kyto, Japan) using KBr optics. 1 H NMR spectra were recorded in CDCl 3 on a Varian Mercury YH-300 MHz spectrophotometer (Palo Alto, CA) and chemical shifts (δ) are given in ppm relative to TMS. Mass spectra were recorded at 70 eV on a Jeol D-300 spectrometer (Tokyo,) and a 3200 QTRAP LC/ MS/MS spectrophotometer (Applied Biosystems, Foster City, CA).…”

Section: Chemistrymentioning

confidence: 99%

“…Nowadays helminth infections are a major medical problem worldwide and there has been a considerable increase in its incidence [1]. It is one of the most frequent sources of human infections particularly in tropical countries like India [2,3].…”

Section: Introductionmentioning

confidence: 99%

Synthesis of some thiazolyl aminobenzothiazole derivatives as potential antibacterial, antifungal and anthelmintic agents

Amnerkar

Bhusari

2011

Journal of Enzyme Inhibition and Medicinal Chemistry

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“…The atom-based molecular vector (" x) used to represent small-to-medium size organic chemicals has been explained in some detail elsewhere [74,81,84,86,104]. In a way parallel to the development of " x, we present the extension to the bond-based molecular vector ( " w).…”

Section: Chemical Information and Bond-based Molecular Vectormentioning

confidence: 99%

Discovery of Novel Trichomonacidals Using LDA‐Driven QSAR Models and Bond‐Based Bilinear Indices as Molecular Descriptors

et al. 2009

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Few years ago, the World Health Organization estimated the number of adults with trichomoniasis at 170 million worldwide, more than the combined numbers for gonorrhea, syphilis, and chlamydia. To combat this sexually transmitted disease, Metronidazole (MTZ) has emerged, since 1959, as a powerful drug for the systematic treatment of infected patients. However, increasing resistance to MTZ, adverse effects associated to high-dose MTZ therapies and very expensive conventional technologies related to the development of new trichomonacidals necessitate novel computational methods that shorten the drug discovery pipeline. Therefore, bond-based bilinear indices, new 2-D bond-based TOMOCOMD-CARDD Molecular Descriptors (MDs), and Linear Discriminant Analysis (LDA) are combined to discover novel antitrichomonal agents. Generated models, using non-stochastic and stochastic indices, are able to classify correctly the 90.11% (93.75%) and the 87.92% (87.50%) of chemicals in the training (test) sets, respectively. In addition, they show large Matthews correlation coefficients (C) of 0.80 (0.86) and 0.76 (0.71) for the training (test) sets, respectively. The result of predictions on the 10% full-out cross-validation test also evidences the quality of both models. In order to test the models predictive power, 12 compounds, already proved against Trichomonas vaginalis (Tv), are screened in a simulated virtual screening experiment. As a result, they correctly classified 9 out of 12 (75.00%) and 10 out of 12 (83.33%) of the chemicals, respectively, which were the most important criteria to validate the models. Finally, in order to prove the reach of TOMOCOMD-CARDD approach and to discover new trichomonacidals, these classification functions were applied to a set of QSAR Comb. Sci. 28, 2009, No. 1, 9 -26 2009 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim 9 * To whom correspondence should be addressed (contact for chem-and bioinformatics methods) ** Contact for biological assays *** Contact for chemical methods Full Paperseight chemicals which, in turn, were synthesized and tested toward in vitro activity against Tv. As a result, experimental observations confirm theoretical predictions to a great extent, since it is gained a correct classification of 87.50% (7/8) of chemicals. Biological tests also show several candidates as antitrichomonals, since almost all the compounds [VAM2-(3 -8)] exhibit pronounced cytocidal activities of 100% at the concentration of 100 mg/mL and at 24 h (48 h) but VAM2 -2: 99.37% (100%), and it is remarkable that these compounds do not show toxic activity in macrophage assays at this concentration. The Quantitative Structure -Activity Relationship (QSAR) models presented here could significantly reduce the number of synthesized and tested compounds as well as could act as virtual shortcuts to new chemical entities with trichomonacidal activity.

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Atom, atom-type and total molecular linear indices as a promising approach for bioorganic and medicinal chemistry: theoretical and experimental assessment of a novel method for virtual screening and rational design of new lead anthelmintic

Cited by 92 publications

References 37 publications

<strong>Multi-target Prediction of Neuroprotective Drugs, Synthesis, Assay, and Theoretical Study of Rasagiline Carbamates</strong>

<strong>Multi-target Prediction of Neuroprotective Drugs, Synthesis, Assay, and Theoretical Study of Rasagiline Carbamates</strong>

Synthesis of some thiazolyl aminobenzothiazole derivatives as potential antibacterial, antifungal and anthelmintic agents

Discovery of Novel Trichomonacidals Using LDA‐Driven QSAR Models and Bond‐Based Bilinear Indices as Molecular Descriptors

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