Anticancer compounds structure-activity relationships

In this chapter, we describe an account of our research on the chemistry and biology of paclitaxel and taxoid anticancer agents (taxoid = taxol-like compound). The topics covered in this chapter include (i) the development of a practical and efficient method for the semisynthesis of paclitaxel and docetaxel using chiral 3-hydroxy-P-lactams as synthetic intermediates, (ii) structure-activity relationship (SAR) studies of various taxoids that led to the discovery of the extremely potent second-generation taxoids, and (iii) biological and conformational studies with the use of fluorine-containing taxoids as probes. ... 

Cancer cell lines are a useful tool in the anticancer research that facilitates knowledge of new cytotoxic compounds, the potency of a drug or the structure-activity relationship such knowledge helps to develop new anticancer compounds. In this way, lots of pharmacological studies carried out with natural and synthetic flavonoids show that these compounds can inhibit the growth of diverse human cancer cell lines but this information has not been compiled and there is very little imderstanding about a possible structure -activity relationship. Some authors have found some structural requirements (that sometimes... 

Abstract Cancer is an important area of interest in the life sciences because it has been a major killer disease throughout human history. Heterocyclic molecules are well known to play a critical role in health care and pharmaceutical drug design. A number of heterocyclic compounds are available commercially as anticancer drugs. Interest in the application of structure-activity relationships has steadily increased in recent decades. Thus, development of the quantitative structure-activity relationship (QSAR) model on the cytotoxicity data of heterocyclic compound series against various cancer ceU lines should be of great importance. In this chapter, an attempt has been made to collect the... 

From the animal screens emerged the set of structure-activity relationships enumerated earlier (Section IV.E.l). Both cisplatin and carboplatin conform to these rules, and to date no compounds with demonstrably better antitumor activity have been tested in humans. The decision to move an experimental drug into the clinic is a difficult one, however, and it may be that molecules such as cis-[Pt(NH3)2(4-Br-py)Cl]Cl (see Section V.D.V.c) would be effective for tumors that are refractive to cisplatin chemotherapy. In any case, the foregoing chain of events, from studying the effects of a compound on cells in culture through animal screens and eventually to humans, constitutes the principal route for introducing a new anticancer drug. The process can take more than a decade. 

In recent years, a number of diterpenoid pyrones and related compounds have been isolated from microorganisms, particularly from fungal strains [1-6]. Several of these natural products have been reported to exhibit a wide variety of biological properties such as insecticidal [1,3c], antihypertensive [3d], bronchospasmolytic [3d], anti-inflammatory [3d], laxative [3d], anticancer [3e], and immunosuppressive activities [3-6]. In most cases, however, further biological studies including structure-activity relationships (SARs) are severely restricted probably because of the limited structural diversity of microorganisms. Consequently, the development of efficient and flexible synthetic methods for this class of natural products and related compotmds is quite desirable and worthwhile from the viewpoint of medicinal chemistry and pharmaceuticals. 

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