Predicting the bioactivity of 2-alkoxycarbonylallyl esters as potential antiproliferative agents against pancreatic cancer (MiaPaCa-2) cell lines: GFA-based QSAR and ELM-based models with molecular docking

• Main Authors: Oluwatoba Emmanuel Oyeneyin, Babatunde Samuel Obadawo, Adesoji Alani Olanrewaju, Taoreed Olakunle Owolabi, Fahidat Adedamola Gbadamosi, Nureni Ipinloju, Helen Omonipo Modamori
• Format: Article
• Language: English
• Published: SpringerOpen 2021-03-01
• Series: Journal of Genetic Engineering and Biotechnology
• Subjects: 2-alkoxycarbonyl esters; Computer-aided drug design; Genetic function approximation; Extreme learning machine; Epidermal growth factor receptor; Molecular docking
• Online Access: https://doi.org/10.1186/s43141-021-00133-2

Abstract Background The number of cancer-related deaths is on the increase, combating this deadly disease has proved difficult owing to resistance and some serious side effects associated with drugs used to combat it. Therefore, scientists continue to probe into the mechanism of action of cancer cells and designing novel drugs that could combat this disease more safely and effectively. Here, we developed a genetic function approximation model to predict the bioactivity of some 2-alkoxyecarbonyl esters and probed into the mode of interaction of these molecules with an epidermal growth factor receptor (3POZ) using the three-dimensional quantitative structure activity relationship (QSAR), extreme learning machine (ELM), and molecular docking techniques. Results The developed QSAR model with predicted (R 2 pred) of 0.756 showed that the model was fit to be validated parameter for a built model and also proved that the developed model could be used in practical situation, R 2 for training set (0.9929) and test set (0.8397) confirmed that the model could successfully predict the activity of new compounds due to its correlation with the experimental activity, the models generated with ELM models showed improved prediction of the activity of the molecules. The lead compounds (22 and 23) had binding energies of −6.327 and −7.232 kcalmol−1 for 22 and 23 respectively and displayed better inhibition at the binding sites of 3POZ when compared with that of the standard drug, chlorambucil (−6.0 kcalmol−1). This could be attributed to the presence of double bonds and the α-ester groups. Conclusion The QSAR and ELM models had good prognostic ability and could be used to predict the bioactivity of novel anti-proliferative drugs.