Synthesis and receptor dependent 4D-QSAR studies of 4,5-dihydro-1,3,4-oxadiazole derivatives targeting cannabinoid receptor

ABSTRACT

Cannabinoid receptor has been shown to be overexpressed in various types of cancers, especially non-small cell lung cancer. As a result, it could be used as novel target for anticancer treatments. Because receptor-dependent 4D-QSAR generates conformational ensemble profiles of compounds by molecular dynamics simulations at the binding site of the enzyme, this work describes the synthesis, biological activity evaluation and 4D-QSAR studies of 4,5-dihydro-1,3,4-oxadiazole derivatives targeting cannabinoid receptor. Compared with WIN55,212–2, compound 5 f showed the best antiproliferative activity. The receptor-dependent 4D-QSAR model was generated by multiple linear regression method using QSARINS. Leave-n-out cross-validation and chemical applicability domain were performed to analyse the independent test set and to verify the robustness of the model. The best 4D-QSAR model showed the following statistics: r² = 0.8487, Q²_LOO = 0.7667, Q²_LNO = 0.7524, and r²_Pred = 0.8358.

KEYWORDS:

• Cannabinoid receptor
• 4D-QSAR
• synthesis
• anticancer
• 4
• 5-dihydro-1
• 3
• 4-oxadiazole

Disclosure statement

No potential conflict of interest was reported by the authors.

Supplementary material

Supplementary data for this article can be accessed at https://doi.org/10.1080/1062936X.2021.1879256.

Additional information

Funding

The project was supported by the Nanchang University Teaching Reform Foundation (NCUJGLX-19-130, NCUJGLX-19-124), Jiangxi Province Science Foundation (20171BAB205104) and the Undergraduate Innovation and Entrepreneurship Foundation (2020CX289).