Early CORMs

These early CORMs lack the characteristics of a regular drug (Section 6) and none of them simultaneously possesses air, water, and plasma stability. Nevertheless, they were extensively studied in biological systems through the last decade. This section reviews the role of different CORMs on several pathological models and their potential therapeutic applications. Figure 6.5 is a graphical summary of this extremely broad activity. 

Contrary to the early CORMs, none of the new potential CORMs reported until 2012 were selected on the basis of their in vivo activity. Instead, the strategy for their design focused mainly on the CO release event (rate, profile, trigger) or the conditions needed to initiate it in a controlled manner. In a metal-based CORM, the CO dissociation from the metal can be initiated in biological settings... 

The CO release from zerovalent [Fe(CO)3L2] and [Mo(CO)sL] complexes, studied by the groups of I. Fairlamb and J. Lyman since 2006 (Figure 6.8), is triggered by oxidative decarbonylation with O2, but is normally preceded by loss or modification of the ancillary hgands. The pyrone rings stabilized Fe(CO)s fragments, and led to the first CORM candidates reported after the early CORMs. The variation of the X substituents on the diene modulates the lability of the Fe-diene bonds and tunes the CO release rate. Recently, substituted... 

These hardy, autumn-flowering corms are not crocuses, despite their common name. Pink, white, or purple, 2 "-4 "tall flowers bloom without foliage, which comes up in early spring and dies off by midsummer. Narrow dark green leaves grow 6"-12" tall. 

Cut away and destroy severely infested plant parts. Use blue sticky traps to monitor and trap pests. Encourage native predators such as pirate bugs, lacewings, and lady beetles. Insecticidal soap sprays give some control of thrips populations, but may affect beneficials as well. To limit thrips infestation, dig corms early in fall and cut off tops before thrips move down into corms. Bag and discard debris. Dust corms with pyrethrin to control thrips in storage. Or soak them in a Lysol solution (IV2 tablespoons in 1 gallon water) for several hours before planting. 

Leaves yellow plant dies early. Cause Dry rot. Other symptoms of this fungal disease include dry, brown or black, corky spots on corms and husk coverings. You may see black fungal growth spots on decayed leaf bases. Plants may turn yellow and die prematurely. Choose corms carefully to avoid infected specimens. Destroy infected plants. Do not replant in same area. Replant only in well-drained soil. 

Plant products have also played a significant role in the treatment of another parasitic disease, amoebiasis. The root and corm extracts of Cephaelis ipecuanhana were traditionally and empirically for the treatment of dysentry and the active ingredient emetine was isolated in 1817. It was not until 1912 that the antiamoebic activity of the alkaloid emetine was placed on a rational basis. Another product cepahaeline proved to be less active than its methyl ester emetine. In the early 1960s the derivative dehydroemetine was shown to be more active against E. histolytica and less toxic than the parent compound. 

Figure 6.1 The early transition metal CORMs tested in vivo.

Miscellaneous Biologically Significant Observations on Early-Stage CORMs... 

Figure 6.5 Therapeutic activity of the early experimental CORMs.

Biological and Therapeutic Results Obtained with the Early-Stage CORMs 1179... 

Beyond the Early-Stage CORMs Strategies for Finding New Candidates 183... 

For instance, topical application of CORM-2 can reduce the chronic epidermal hyperplasia accompanying tumor outgrowth (photocarcinogenesis) induced by UVB (290-320 nm) radiation in hairless mouse [105], being a potential anticancer drug at early stages of tumor development. 

At Alfama, m late 2008, it became obvious that practical use demanded new CORMs. To be acceptable, such CORMs must be drug-Uke, that is, stable in air, water, and blood soluble in water toxicologically safe therapeutically potent and possessing a reasonable pharmacokinetic profile. Moreover, they must be targeted to the tissues in need in order to become sufficiently effective at low doses, to decrease metal and CO toxicity issues. None of the early or other reported CORMs exhibited this complete set of properties. However, the... 

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