There are several drugs to treat breast cancer; nevertheless, some of these drugs can produce some adverse effects such as bronchospasm, thinning, and angioedema. In the search for new therapeutic alternatives, some drugs have been developed using different reagents, which are expensive and difficult to handle. This study aimed to synthesize two steroid derivatives (compounds 4 and 5) from estrone using chemical strategies. Besides, a theoretical study was carried out to evaluate the interaction of 4 and 5 with 17β-hydroxysteroid dehydrogenase enzyme (6mnc protein). It is important to mention that estrone and fisetin were used as a control in a docking model. The results showed that compound 4 has a higher affinity by 6mnc protein surface compared with estrone, fisetin, and compound 5. In conclusion, these data suggest that compound 4 could be a good candidate for breast cancer treatment.