A QSAR study to predict the survival motor neuron promoter activity of candidate diaminoquinazoline derivatives for the potential treatment of spinal muscular atrophy

ABSTRACT

Spinal Muscular Atrophy is a genetic neuromuscular disease that leads to muscle weakness and atrophy and it is characterized by the loss of α-motor neurons in the spinal cord’s anterior horn cells. The disease appears due to low levels of the survival motor neuron protein. There are continuing clinical trials for the treatment of Spinal Muscular Atrophy. Quinazoline–based compounds are promising since they were tested on fibroblasts derived from the patients and found to increase the survival motor neuron protein levels. In this study, using multiple linear regression, we generated robust and valid quantitative structure- activity relationship models to predict the survival motor neuron–2 promoter activity of the new candidate compounds using the experimental survival motor neuron–2 promoter activity values of 2,4–diaminoquinazoline derivatives taken from the literature. The novel compounds designed by combining the pyrido[1,2–α]pyrimidin–4–one moeity of the known drug Risdiplam with that of 2,4 – diaminoquinazoline scaffold were predicted to exhibit strong promoter activities.

KEYWORDS:

• SMA
• SMN protein
• QSAR
• diaminoquinazoline
• Risdiplam
• MLR

Acknowledgements

We thank Prof. Paola Gramatica (University of Insubria, Italy) for providing the QSARINS software. SSE would like to acknowledge Marmara University Scientific Research Project Commission (BAPKO) for supporting the Computational Chemistry Laboratory.

Disclosure statement

No potential conflict of interest was reported by the author(s).

Supplementary material

Supplemental data for this article can be accessed at: https://doi.org/10.1080/1062936X.2023.2200975

Additional information

Funding

The author(s) reported there is no funding associated with the work featured in this article.