Recent Anticancer Cytotoxic Agents

Abstract

In spite of the impressive progress in diagnosis, surgery and therapy that occurred since the Sixties, the overall cancer mortality is still high and the medical need is largely unmet. A number of innovative strategies, aimed to target malignant abnormalities of tumor cells are in development and begin to give important results. In alternative, angiogenesis inhibition has been addressed with the aim to limit the tumor ability to grow and metastasize. However, it will likely take some years to fully define the therapeutic role of different innovative drugs. Therefore, cytotoxic drugs will continue to represent a chief part of the therapy in the forthcoming years, possibly in combination with innovative agents addressing molecular targets. Most important traditional chemotherapeutic drugs or investigational anticancer agents were derived from natural sources also through synthetic structural modifications. In the Nineties, taxanes and camptothecins represented important success stories of this approach, while among DNA interacting agents anthracyclines continued to represent a structural platform for discovering new drugs and DNA minor groove binders represented a new field of investigation. Combinatorial chemistry combined with high-throughput screening programs are an important source of totally synthetic new agents, however, it should not be disregarded the fact that nature already performed combinatorial chemistry and leads selection through the ages. New natural or semisynthetic agents acting as tubulin stabilizers or DNA interactive agents of various mechanisms of action are presently investigated and will probably continue to give important contribution to cancer therapy in the near future. In this review, the medicinal chemistry and the development status of these anticancer cytotoxic agents are focused and discussed.

Antiproliferative activity of selected medicinal plants of Jordan against a breast adenocarcinoma cell line (MCF7)

“…It is worthy to mention the vivid current interest in discovery of natural drugs for cancer treatment and chemoprevention [4,5]. Huge number of plant species is screened and bioassayed for this purpose worldwide [6][7][8][9][10][11][12][13][14][15][16][17].…”

“…The estimated worldwide incidence of different carcinomas is about 10 million; half of these are in developed countries [13]. Among the cancer patients in the USA, the use of complementary and alternative medicine, represented mainly by plants, ranges between 30-75% [6].…”

A “click chemistry” approach to the straightforward synthesis of new 4-aryl-1,2,3-triazolocarbanucleosides

“…Other nucleoside analogues owning 5-membered heterocyclic bases, such as imidazoles and triazoles, have displayed interesting biological properties; for instance, brenedin (Mizoribine as an immunosuppressor for the treatment of transplant patients 2 and EICAR (3, Figure 1), causes depletion of purine nucleotides resulting in a broad spectrum of activity against RNA and DNA viruses and tumour cell proliferation. 3 In this context, a great number 1,2,3-triazole derivatives have shown a great potential as antiviral, antibacterial or antiproliferative agents, 4 Furthermore, we and others have recently reported several examples of 1,2,3-triazolyl carbanucleosides owning promising biological activities ( Figure 2). 7 For example, compound (±)-6 (R = 2-C 6 H 4 OMe) exhibited specific inhibitory potential against TK + VZV (EC 50 = 11 μM), 8 7 was found to own moderate activity against HIV-1 (IC 50 = 43.8 μM), 9 and 8 In recent times we have started a research program devoted to the synthesis and biological evaluation as antiviral and antitumoral agents of carbanucleosides produced using, in some extent, the postulates of "click chemistry".…”

Synthesis and Preliminarily Cytotoxicity to A549, HCT116 and MCF-7 Cell Lines of Thieno[2,3-d]pyrimidine Derivatives Containing Isoxazole Moiety

“…Cancer is the leading cause of death after cardiovascular disease, and the relative mortality rate caused by cancer is still very high even in developed countries, statically evident around 6-7 million new cases per year [1]. Lung cancer is the number one cause of cancer related death globally, with an estimated 13% of total cases and accounting for 18% of total deaths worldwide in 2008 [2].…”