A novel mithramycin analogue with high antitumor activity and less toxicity generated by combinatorial biosynthesis.

Journal of Medicinal Chemistry
Luz Elena NúñezCarmen Méndez

Abstract

Mithramycin is an antitumor compound produced by Streptomyces argillaceus that has been used for the treatment of several types of tumors and hypercalcaemia processes. However, its use in humans has been limited because of its side effects. Using combinatorial biosynthesis approaches, we have generated seven new mithramycin derivatives, which differ from the parental compound in the sugar profile or in both the sugar profile and the 3-side chain. From these studies three novel derivatives were identified, demycarosyl-3D-β-d-digitoxosylmithramycin SK, demycarosylmithramycin SDK, and demycarosyl-3D-β-d-digitoxosylmithramycin SDK, which show high antitumor activity. The first one, which combines two structural features previously found to improve pharmacological behavior, was generated following two different strategies, and it showed less toxicity than mithramycin. Preliminary in vivo evaluation of its antitumor activity through hollow fiber assays, and in subcutaneous colon and melanoma cancers xenografts models, suggests that demycarosyl-3D-β-d-digitoxosylmithramycin SK could be a promising antitumor agent worthy of further investigation.

References

Sep 1, 1995·Journal of Molecular Biology·M SastryD J Patel
Jul 6, 1993·Biochemistry·M Sastry, D J Patel
Jan 23, 1999·Journal of Natural Products·S E WohlertJ Rohr
Aug 30, 2000·Biological & Pharmaceutical Bulletin·M TagashiraY Ohtake
Oct 3, 2002·Nature Reviews. Cancer·James E Darnell
Jun 6, 2003·Bioorganic & Medicinal Chemistry·Mohd Ayoub MirDipak Dasgupta
Oct 19, 2004·Oncogene·George Koutsodontis, Dimitris Kardassis
Oct 19, 2004·Oncogene·G Steven Martin
Oct 8, 2005·European Journal of Cancer : Official Journal for European Organization for Research and Treatment of Cancer (EORTC) [and] European Association for Cancer Research (EACR)·Stephen Safe, Maen Abdelrahim
Oct 3, 2006·Applied Microbiology and Biotechnology·Felipe LombóCarmen Méndez
Feb 21, 2007·Journal of Natural Products·David J Newman, Gordon M Cragg
Mar 21, 2007·Nucleic Acids Research·Francisca BarcelóJosé Portugal
Oct 3, 2007·Clinical Cancer Research : an Official Journal of the American Association for Cancer Research·Doris Germain, David A Frank
Jan 17, 2008·Journal of Natural Products·Irfan BaigJürgen Rohr
Nov 7, 2008·Chembiochem : a European Journal of Chemical Biology·Felipe LombóCarmen Méndez
Apr 21, 2009·Methods in Enzymology·Felipe LombóCarmen Méndez
Jun 18, 2010·Journal of Neuro-oncology·Janina SeznecUlrike Naumann
Dec 1, 2010·Expert Opinion on Therapeutic Patents·Brent D G PagePatrick T Gunning
May 6, 2011·The Journal of Neuroscience : the Official Journal of the Society for Neuroscience·Sama F SleimanRajiv R Ratan
Jun 1, 2011·Archivum Immunologiae Et Therapiae Experimentalis·Jacek WilczynskiMalgorzata Czyz
Jun 10, 2011·Journal of the National Cancer Institute·Patrick J GroharLee J Helman

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Citations

Sep 6, 2013·Journal of Industrial Microbiology & Biotechnology·Nguyen Huy Thuan, Jae Kyung Sohng
Dec 4, 2012·Journal of Chemical Information and Modeling·Paola BisignanoAndrea Cavalli
Dec 25, 2013·PloS One·Lidija K GorsicM Eileen Dolan
Dec 3, 2014·Journal of Inorganic Biochemistry·Shibojyoti LahiriDipak Dasgupta
May 12, 2015·Pharmacology & Therapeutics·Carolina VizcaínoJosé Portugal
Jun 17, 2015·Toxicology in Vitro : an International Journal Published in Association with BIBRA·Carolina VizcaínoJosé Portugal
Sep 4, 2015·Chemical Society Reviews·Dong-Mei LiangJian-Jun Qiao
Mar 5, 2015·Chemical Society Reviews·Sherif I ElshahawiJon S Thorson
Mar 31, 2019·Biomedical Chromatography : BMC·Joseph M EckenrodeMarkos Leggas
Aug 24, 2019·Nature Communications·Victoria García-MoralesBernardo Moreno-López
Jun 17, 2020·Biopolymers·José Portugal
Jul 21, 2020·Applied Microbiology and Biotechnology·Jan KormanecDagmar Homerova
Mar 17, 2016·Clinical Cancer Research : an Official Journal of the American Association for Cancer Research·Christy L OsgoodPatrick J Grohar
Jan 16, 2021·Biomedicines·David SchweerJill Kolesar
May 13, 2021·Seminars in Cancer Biology·Chakrabhavi Dhananjaya MohanKanchugarakoppal S Rangappa
Jun 30, 2021·Life Sciences·Parichehr HassanzadehFatemeh Rostami
Sep 18, 2020·The Journal of Organic Chemistry·Katelyn V BrownS Eric Nybo

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