MCDCalc: Markov Chain Molecular Descriptors Calculator for Medicinal Chemistry

Paula       Carracedo-Reboredo; Ramiro       Corona; Mikel       Martinez-Nunes; Carlos       Fernandez-Lozano; Georgia       Tsiliki; Haralambos       Sarimveis; Eider       Aranzamendi; Sonia       Arrasate; Nuria       Sotomayor; Esther       Lete; Cristian    Robert    Munteanu; Humbert       González-Díaz

doi:10.2174/1568026620666191226092431

Abstract

Aims: Cheminformatics models are able to predict different outputs (activity, property, chemical reactivity) in single molecules or complex molecular systems (catalyzed organic synthesis, metabolic reactions, nanoparticles, etc.).

Background: Cheminformatics models are able to predict different outputs (activity, property, chemical reactivity) in single molecules or complex molecular systems (catalyzed organic synthesis, metabolic reactions, nanoparticles, etc.).

Objective: Cheminformatics prediction of complex catalytic enantioselective reactions is a major goal in organic synthesis research and chemical industry. Markov Chain Molecular Descriptors (MCDs) have been largely used to solve Cheminformatics problems. There are different types of Markov chain descriptors such as Markov-Shannon entropies (Shk), Markov Means (Mk), Markov Moments (πk), etc. However, there are other possible MCDs that have not been used before. In addition, the calculation of MCDs is done very often using specific software not always available for general users and there is not an R library public available for the calculation of MCDs. This fact, limits the availability of MCMDbased Cheminformatics procedures.

Methods: We studied the enantiomeric excess ee(%)[Rcat] for 324 α-amidoalkylation reactions. These reactions have a complex mechanism depending on various factors. The model includes MCDs of the substrate, solvent, chiral catalyst, product along with values of time of reaction, temperature, load of catalyst, etc. We tested several Machine Learning regression algorithms. The Random Forest regression model has R2 > 0.90 in training and test. Secondly, the biological activity of 5644 compounds against colorectal cancer was studied.

Result: We developed very interesting model able to predict with Specificity and Sensitivity 70-82% the cases of preclinical assays in both training and validation series.

Conclusion: The work shows the potential of the new tool for computational studies in organic and medicinal chemistry.

Keywords: Molecular descriptors, Markov chains, Singular values, Online tool, R-script, Chiral catalyst, Enantioselectivity, α-Amidoalkylation reactions, Biological activity, Colorectal cancer.

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Graphical Abstract

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DOI https://dx.doi.org/10.2174/1568026620666191226092431	Print ISSN 1568-0266
Publisher Name Bentham Science Publisher	Online ISSN 1873-4294

Current Topics in Medicinal Chemistry

MCDCalc: Markov Chain Molecular Descriptors Calculator for Medicinal Chemistry

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