Synthesis and Anti-Cancer Activity Evaluation of New Dimethoxylated Chalcone and Flavanone Analogs

• Published in: Archiv der Pharmazie (Weinheim) 2014-11, Vol.347 (11), p.853-860
• Main Authors: Ketabforoosh, Shima H. M. E., Kheirollahi, Asma, Safavi, Maliheh, Esmati, Nasim, Ardestani, Sussan K., Emami, Saeed, Firoozpour, Loghman, Shafiee, Abbas, Foroumadi, Alireza
• Format: Article
• Language: English
• Subjects: Anti-cancer agents; Antineoplastic Agents - chemical synthesis; Antineoplastic Agents - pharmacology; Apoptosis; Apoptosis - drug effects; Breast cancer; Cell Survival - drug effects; Chalcone; Chalcones - chemical synthesis; Chalcones - pharmacology; Cytotoxicity; Dose-Response Relationship, Drug; Drug Design; Flavanone; Flavanones - chemical synthesis; Flavanones - pharmacology; Flow Cytometry; Humans; Inhibitory Concentration 50; MCF-7 Cells; Medical research; Microscopy, Fluorescence; Molecular Structure; Structure-Activity Relationship
• ISSN: 0365-6233; 1521-4184
• DOI: 10.1002/ardp.201400215

A novel series of chalcones and flavanones discriminated by the presence of a 3,4‐dimethoxyphenyl moiety in their structures were synthesized as anti‐cancer agents. The cytotoxicity evaluation of the analogs against the MCF‐7, MDA‐MB‐231 (human breast cancer), and SK‐N‐MC (human neuroblastoma) cell lines demonstrated that the introduction of a halogen on the 3,4‐dimethoxyphenyl part of both series and the attachment of a pyrrolidinylethoxy group on the C‐7 position of the flavanone derivatives increased their activity. Indeed, 3‐halogenated chalcones (1c and 1d) were more potent than the standard drug etoposide against all tested cell lines. Fluorescence microscopy and flow cytometry analyses confirmed that the anti‐cancer effect of the most potent compounds 1c and 1d occurs via apoptosis induction. A novel series of 3,4‐dimethoxy‐chalcones and flavanones were synthesized as cytotoxic agents. 3‐Halogenated chalcones (1c and 1d) showed the highest cytotoxic activity and induced apoptosis in cancer cells.