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

Sabuncu Gürses G., ERDEM S., Saçan M.

SAR and QSAR in environmental research, cilt.34, sa.3, ss.247-266, 2023 (SCI-Expanded) identifier identifier

  • Yayın Türü: Makale / Tam Makale
  • Cilt numarası: 34 Sayı: 3
  • Basım Tarihi: 2023
  • Doi Numarası: 10.1080/1062936x.2023.2200975
  • Dergi Adı: SAR and QSAR in environmental research
  • Derginin Tarandığı İndeksler: Science Citation Index Expanded (SCI-EXPANDED), Scopus, Academic Search Premier, Aquatic Science & Fisheries Abstracts (ASFA), BIOSIS, Biotechnology Research Abstracts, CAB Abstracts, Chemical Abstracts Core, EMBASE, Environment Index, MEDLINE, Pollution Abstracts, Veterinary Science Database
  • Sayfa Sayıları: ss.247-266
  • Anahtar Kelimeler: diaminoquinazoline, MLR, QSAR, Risdiplam, SMA, SMN protein
  • Marmara Üniversitesi Adresli: Evet

Özet

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.