Abstract
Chemically diverse heterocyclic chalcones were prepared and evaluated for cytotoxicity, aiming to push forward potency and selectivity. They were tested against rhabdomyosarcoma (RMS) and noncancerous cell line (LLC-PK1). The influence of heteroaryl patterns on rings A and B was studied. Heterocycle functionalities on both rings, such as phenothiazine, thiophene, furan and pyridine were evaluated. Notably, the introduction of three methoxy groups at positions 3, 4, 5 on ring B appears to be critical for cytotoxicity. The best compound, with potent and selective cytotoxicity (IC50 = 12.51 μM in comparison with the value 10.84 μM of paclitaxel), contains a phenothiazine moiety on ring A and a thiophene heterocycle on ring B. Most of the potential compounds only show weak cytoxicity on the noncancerous cell line LLC-PK1.
Highlights
Statistics indicate that cancer is the second most frequent cause of death in the U.S only after cardiovascular disease and the leading cause of death in the UK [1,2]
The synthesis of all the target compounds was accomplished by classical Claisen-Schmidt condensation between an acetophenone derivative and a corresponding aryl aldehyde in condensation between an acetophenone derivative and a corresponding aryl aldehyde in methanolic/KOH at room temperature, as depicted in Scheme 1 [31,32,33]
The cytotoxicity assay results are shown in Table
Summary
Statistics indicate that cancer is the second most frequent cause of death in the U.S only after cardiovascular disease and the leading cause of death in the UK [1,2]. Some of the dominant drawbacks of present anticancer drug therapy involve their lack of significant greater toxicity towards cancer cells in comparison with normal tissue and the rise of multi-drug resistance. Tumor-selective cytotoxic agents whose structures are sufficiently different from anticancer medication currently on the market are highly sought. Soft tissue sarcomas constitute a heterogeneous group of neoplasms which accounts for approximately 7% of all cancer cases in patients under the age of 20 [3,4,5]. Chemotherapy using well-known anticancer medicines including vinscristine, dactinomycin and cyclophosphamide is mostly indicated for all patients with RMS [3,6]. Other agents such as melphalan, Molecules 2016, 21, 329; doi:10.3390/molecules21030329 www.mdpi.com/journal/molecules
Sign-in/Register to view highlights & summary Talk to us
Join us for a 30 min session where you can share your feedback and ask us any queries you have
Schedule a callDisclaimer: All third-party content on this website/platform is and will remain the property of their respective owners and is provided on "as is" basis without any warranties, express or implied. Use of third-party content does not indicate any affiliation, sponsorship with or endorsement by them. Any references to third-party content is to identify the corresponding services and shall be considered fair use under The CopyrightLaw.
