Listro Roberta, Stotani Silvia, Rossino Giacomo, Rui Marta, Malacrida Alessio, Cavaletti Guido, Cortesi Michela, Arienti Chiara, Tesei Anna, Rossi Daniela, Giacomo Marcello Di, Miloso Mariarosaria, Collina Simona
Medicinal Chemistry and Pharmaceutical Technology Section, Department of Drug Sciences, University of Pavia, Pavia, Italy.
Medicinal Chemistry, Taros Chemicals GmbH and Co. KG, Dortmund, Germany.
Front Chem. 2020 Jun 30;8:495. doi: 10.3389/fchem.2020.00495. eCollection 2020.
Despite the fact that significant advances in treatment of common cancers have been achieved over the years, orphan tumors still represent an important unmet medical need. Due to their complex multifactorial origin and limited number of cases, such pathologies often have very limited treatment options and poor prognosis. In the search for new anticancer agents, our group recently identified , a Sigma receptor modulator endowed with proteasome inhibition activity. This compound showed antiproliferative activity toward different cancer cell lines, among them glioblastoma (GB) and multiple myeloma (MM), two currently unmet medical conditions. In this work, we directed our efforts toward the exploration of chemical space around to identify new active compounds potentially useful in cancer treatment. Thanks to a combinatorial approach, we prepared 41 derivatives of the compound and evaluated their cytotoxic potential against MM and GB. Three novel potential anticancer agents have been identified.
尽管多年来在常见癌症的治疗方面取得了重大进展，但罕见肿瘤仍然代表着一项重要的未满足医疗需求。由于其复杂的多因素起源和病例数量有限，此类病症的治疗选择往往非常有限，预后也很差。在寻找新型抗癌药物的过程中，我们团队最近发现了一种具有蛋白酶体抑制活性的西格玛受体调节剂。该化合物对不同癌细胞系表现出抗增殖活性，其中包括胶质母细胞瘤（GB）和多发性骨髓瘤（MM），这两种病症目前尚无有效的治疗方法。在这项工作中，我们致力于探索该化合物周围的化学空间，以确定可能对癌症治疗有用的新活性化合物。通过组合方法，我们制备了该化合物的41种衍生物，并评估了它们对MM和GB的细胞毒性潜力。已鉴定出三种新型潜在抗癌药物。
