Synthetic biology cancer treatment

The extraordinary biological activity of epothilones has spurred interest of scientists around the world. Indeed, several epothilones and many derivatives are currently in different phases of clinical trials for the treatment of various forms of cancer. Also the synthetic community has given a great deal of attention to these remarkable compounds, probably more than to any other compound in the last ten years. This is not very surprising, because in comparison to paclitaxel (which until recently was one of the main success stories of natural products research), the epothilones have a relatively simple structure, which allows easier modification, and they display higher in vitro activity as well as better pharmacokinetic properties. 

A recombinant IFN-P, IFN-pia (Rebif Serono and Avonex Biogen) is produced for commercial use in Chinese hamster ovary (CHO) cells. A synthetic mutant produced in bacteria has a substitution of serine for cysteine at amino acid 17, yielding IFN-pib Betaseron Berlex). Both IFN-pia and IFN-pib are approved by the FDA for treatment of multiple sclerosis (MS) and have shown comparable biological activity (see Section 7.3). In vivo IFN-a2 and IFN-alb show comparable biological activity as well as similar side effects [54,55]. However, IFN-P is eliminated faster, resulting in no detectable serum peak levels [56]. The clinical consequence of this is not known. Objective responses, whether partial or complete tumor regression, have been documented in patients with carcinoma of the breast, hairy-cell leukemia, and non-small-cell lung cancer [57,58]. 

D-Oleandrose and L-olivomycose (3-C-methyl-L-olivose) together with 6-de-oxy-4- O-methyl-L-glucosc are constituents of the oligosaccharide in apoptolidin, isolated from Nocardiopsis sp., which was the subject of intense synthetic and biological investigation because of its potential for the treatment of cancer.151 155... 

He has served as the director of the Istituto Farmacochimico (March 1995-June 1999) and director of the Dipartimento Farmacochimico Toss. Biol. (July 1999-December 2004 and July 2005-to date). He is responsible for ERASMUS exchanges of the Faculty of Pharmacy of the University of Palermo for the research sector Synthetic Analogues of Natural Structure of Biological Interest of the ICTPN-CNR in a scientific capacity (January 1994—December 1998). He has been Member of the Drug Discovery Committee of the European Organization for Research and Treatment of Cancer, the Societa Chimica Italiana, Member, and the International Society of Heterocyclic Chemistry (which he has also served in the capacity of vice-president for the period 2004—05). He is a scientific editor of the journal ARKIVOC. 

For example, the new etoposide analog GL-311, possessing a C-4/ -aminoaniline substitution, is currently in phase II clinical trials for various anticancer treatments. This compound is a more potent inhibitor of proliferation of refractory cancer cells than etoposide [34]. Attempts to increase the biological activity of GL-311 by di- and tri- substitution of the aniline ring have produced derivatives up to 10 times as potent as etoposide [35]. Other such compounds have proved at least as active as etoposide as anticancer agents these include alkylamino-substituted derivatives [36, 37] and synthetic acetyl salicylic acid, 2-... 

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