Synthesis and in vitro antitumour activity of carboplatin analogues containing functional handles compatible for conjugation to drug delivery systems |
| |
| Affiliation: | 1. Institut des Biomolécules Max Mousseron, UMR 5247, CNRS, Université de Montpellier, ENSCM, UFR des Sciences Pharmaceutiques et Biologiques, 15 Avenue Charles Flahault, 34093 Montpellier Cedex 5, France;2. Institut de Recherche en Cancérologie de Montpellier, INSERM, Université de Montpellier, Institut Régional du Cancer de Montpellier, 208 Avenue des Apothicaires, 34298 Montpellier Cedex 5, France;3. Nuclear Medicine Department, Montpellier Cancer Institute (ICM), University of Montpellier, 208 Avenue des Apothicaires, 34298 Montpellier Cedex 5, France;1. Department of Chemistry and Virginia Tech Center for Drug Discovery, Virginia Tech, Blacksburg, VA 24061, United States;2. Department of Biochemistry and Molecular Biology and Center for Tropical and Emerging Global Diseases (CTEGD), University of Georgia, 120 Green Street, Athens, GA 30602, United States;1. Department of Patho-Functional Bioanalysis, Graduate School of Pharmaceutical Sciences, Kyoto University, 46-29 Yoshida Shimoadachi-cho, Sakyo-ku, Kyoto 606-8501, Japan;2. Department of Diagnostic Imaging and Nuclear Medicine, Graduate School of Medicine, Kyoto University, 54 Shogoinkawara-cho, Sakyo-ku, Kyoto 606-8507, Japan;1. Department of Chemistry, Guru Nanak Dev University, Amritsar 143005, Punjab, India;2. Institut de Recherche en Infectiologie (IRIM) de Montpellier, CNRS, UMR 9004 Université de Montpellier, France;3. INSERM, IRIM, 34293 Montpellier, France;4. School of Chemistry and Physics, University of KwaZulu-Natal, P/Bag X54001, Westville, Durban, South Africa;1. Department of Ultrasound Diagnosis, Xijing Hospital, Fourth Military Medical University, Xi''an 710038, China;2. Department of Pharmaceutics, School of Pharmacy, Fourth Military Medical University, Xi’an 710032, China;1. Department of Technology and Biotechnology of Drugs, Faculty of Pharmacy, Jagiellonian University Medical College, Medyczna 9, Kraków 30-688, Poland;2. Department of Medical Microbiology and Immunobiology, Faculty of Medicine, University of Szeged, Dóm tér 10, 6720 Szeged, Hungary;3. Institute of Pharmaceutical and Medicinal Chemistry, Heinrich-Heine-University Düsseldorf, Universitaetsstr. 1, 40225 Düsseldorf, Germany;1. Hanoi University of Pharmacy, 13-15 Le Thanh Tong, Hanoi, Viet Nam;2. College of Pharmacy, Chungbuk National University, 194-31, Osongsaengmyung-1, Heungdeok, Cheongju, Chungbuk 28160, Republic of Korea;3. Laboratory Animal Resource Center, Korea Research Institute of Bioscience and Biotechnology, Cheongju, Chungbuk, Republic of Korea;4. Faculty of Pharmacy, PHENIKAA University, Hanoi 12116, Viet Nam;5. PHENIKAA Institute for Advanced Study (PIAS), PHENIKAA University, Hanoi 12116, Viet Nam |
| |
| Abstract: | We describe herein the synthesis of a series of carboplatin derivatives with different functional groups at position 3 of the cyclobutane ring. This pharmacomodulation approach aims at facilitating the vectorisation of these analogues, via their subsequent conjugation to a drug delivery system. Five different derivatives bearing a hydroxy, keto, iodo, azido or amino function at position 3 were synthesised. One of these compounds was coupled to a bifunctional maleimide-containing linker. All compounds were tested in vitro for their cytotoxicity on four different cell lines including two platinum-resistant colorectal cancer cell line (SK-OV-3, HCT116, D3E2, D5B7) using an MTS assay. Overall, the tested compounds were up to six times more potent than carboplatin, especially on D5B7 human colorectal cancer cells. We demonstrated that these modifications led to potent analogues which are compatible with conjugation to a drug delivery system. |
| |
| Keywords: | Carboplatin derivatives Vectorisation Anticancer activity Platinum resistance MTS assay |
| 本文献已被 ScienceDirect 等数据库收录！ |
|
