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Synthesis and antiproliferative activity evaluation of B-norcholesterol-6-amide compounds

Background: The structure modification of steroids is commonly used to change the biological activity of steroids in medicinal chemistry. In recent years, it has been found that some derivatives derived from the structural modification of cholesterol display good inhibitory activity against tumor cell proliferation in vitro.

Methods: Using cholesterol as the starting material, different types of B-norcholesterol-6-amide derivatives were synthesized by the reaction of 6-carboxyl-B-norcholesterol with different alkyl amines or 6-amino-B-norcholesterol with different acyl chlorides. The inhibitory activity of compounds on the proliferation of tumor cell lines was investigated by the MTT method.

Results: The results showed that the B-norcholesterol-6-amide compounds displayed distinct cytotoxicity against Sk-Ov-3 cells but caused no obvious damage against HEK-293T cells. Additionally, the steroidal amide derivatives formed from 6-amino-B-norcholesterol showed stronger cytotoxicity than those produced from 6-carboxyl-B-norcholesterol. Specially, compounds with chloroalkyl structure displayed significant inhibitory activity against all tumor cells tested. Among them, compounds 19-21 showed cytotoxicity like 2-methoxyestradiol as a positive control, and the IC50 value of compound 20 on HeLa cells was 3.9 μM.

Conclusion: After introducing chloroalkyl acyl groups into 6-position of 6-amino-B-norcholesterol, the cytotoxicity of resulting B-norcholesterol-6-amide compounds can be greatly enhanced.

Comments：

B-norcholesterol-6-amide derivatives synthesized from 6-amino-B-norcholesterol with different acyl chlorides were found to have strong cytotoxicity against tumor cells with chloroalkyl structures displaying the strongest inhibitory activity, with compound 20 having an IC50 value of 3.9 μM against HeLa cells.

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