Biological inotropic activity

Apart from AP-A, the best characterized of these polypeptides with respect to its biological activity is Anemonia sulcata toxin II (ATX II) [19]. This molecule is also cardioactive [28], as would be expected from its similarity to AP-A. Renaud et al. [29] have compared the activities of a number of sea anemone and scorpion toxins on isolated rat atria and found that anthopleurin-B (AP-B, also known as Ax II) had the highest potency and the greatest margin between the concentrations necessary for maximal inotropic activity and for provoking arrhythmias (0.3 versus 10 n . It was also found that sodium channels of rat cardiac cells in culture, which have a low affinity for tetrodotoxin (TTX), have a particularly high affinity for Type 1 anemone toxins [29], whereas Type 2 toxins [30] and scorpion toxins [31] had similar affinities for TTX-sensitive and TTX-insensitive channels in rat neuroblastoma cells and skeletal myotubes, respectively. 

The weakening or even loss of potency in such derivatives of C[D-trans steroids has led to the tacit opinion that CfD-trans steroids as such cannot elicit inotropic activity and serve as potential cardiac drug candidates. Most remarkably, however, certain steroid representatives with trans junction of the rings C and D have recently been demonstrated to evolve similar or even higher interaction energies with human NaVK -ATPase compared with their CfD-cis counterparts [88]. This discovery has prompted studies on the impact of glycosidation on the biological activity of CfD-trans steroids in view of their possible suitability to serve as a novel type of pharmacophoric lead structure [22,183,184]. This is evaluated below. 

A wide variety of compounds containing the basic 1-pyrindine skeleton have found applications in the biomedical field.50-52, 102 Compounds 52 and 53 described above, possess valuable biological activities similar to mepyrapone which has been found to act as a specific 1 l-j8-hydroxylase inhibitor in the biosynthesis of corticoid hormones in man as well as in animals.51 Antishock activity has been found in a series of octahydro- and decahydrobenzo[a]cyclopenta[/]quinolizenes (12) and (13).151tt The cardiovascular and potent antishock properties of 2,3,3a,5,6,ll,12,12a-octahydro-8-hydroxy-l/7-benzo[a]cyclopenta[/]-quinolizinium bromide (12a),151b as well as its positive inotropic effect on the cat papillary muscle preparation,1510 have been reported. Methods of synthesis for a series of these compounds and tests of their relative antishock activity have been described.151 Although some compounds were active, comparison of these results pointed up the lack of structure-activity relationships in the seven compounds tested. 

Leukotrienes C4 and D4 also have very pronounced effects on the cardiovascular system. They are, for example, very effective coronary artery vasoconstrictors. A number of indirect effects have also been attributed to LTC4 and LTD4. For example, these agents effect the secretion of mucous in the respiratory tract and cause negative inotropic effects in mammalian heart preparations. Many other biological activities have been associated with the peptido-leukotrienes. 

The destruxins, cychc peptides containing five amide bonds and one ester bond, were first isolated hyKodaira in 1961 from Oospora destructor 760), hence the naming of these compounds. Well-documented biological effects are insecticidal and phytotoxic activities 758). Furthermore, also antitumor, inotropic, or enzyme inhibitory effects are reported. Destruxin E, for example, was synthesized in 2010 761). 

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