Antibacterial properties in vivo

In 1935, a red dye called Prontosil, 30, was discovered to have antibacterial properties in vivo (i.e., when given to laboratory animals). No antibacterial effect was observed in vitro (i.e., Prontosil could not kill bacteria grown in a test tube). This result remained a mystery until it was discovered that Prontosil was not in fact the antibacterial agent. Instead, it was found that the Prontosil was metabolized by bacteria present in the small intestine of the test animal, and broken down to sulfanilamide 31 [6]. 

ANTIBACTERIAL PROPERTIES in VIVO Studies in Experimental Animals... 

In spite of the rationale on which the testing of dyestuffs as antibiotics rested subsequent research re vealed that the antibacterial properties of Prontosil had nothing at all to do with its being a dye In the body Prontosil undergoes a reductive cleavage of its azo linkage to form sulfanilamide which is the sub stance actually responsible for the observed biological activity This is why Prontosil is active in vivo but not in vitro... 

Extensive early studies of in vitro and in vivo structure-activity relationships within the leucomycin family revealed correlations between the number and type of O-acyl substituents and the compounds antibacterial potency, efficacy in treating experimental infections, and serum antibiotic concentrations [26]. Consequently, esterification of all hydroxyl groups within several leucomycin-related macrolides was conducted to find derivatives with better antibiotic activity and pharmaceutical properties (such as greater water solubility and masking their extremely bitter taste). From such investigations with midecamycin, miokamycin was synthesized and characterized as a useful new macrolide antibiotic [24, 27]. It has now been commercially launched in several countries [5]. 

Roberts WR, Addy M. Gomparlson of the in vivo and in vitro antibacterial properties of antiseptic mouthrinses containing chlorhexidine, alexidine, cetylpyridinium chloride and hexetidine - relevance to mode of action. J Clin Periodontol 1981 8(4) 295-310. 

Pharmacokinetic properties of the cephalosporins depend to a considerable extent on their chemical nature, e.g. the substituent R2. The 3-acetoxymethyl compounds such as cephalothin, cephapirin and cephacetrile are converted in vivo by esterases to the antibacterially less active 3-hydroxymethyl derivatives and are excreted partly as such. The rapid excretion means that such cephalosporins have a short half-life in the body. Replacement of the 3-acetoxymethyl group by a variety of groups has rendered other cephalosporins much less prone to esterase attack. For example, cephaloridine has an internally compensated betaine group at position 3 (R2) and is metabolically stable. 

Pronestyl " procainamide, pronetalol pronethalol. pronethalol [ban] (pronetalol [inn] Alderlin " Nethalide ") is a p-ADRENOCEPTOR antagonist with antianginal, antiarrhythmic and anthiypertensive properties. It was the first p-blocker used clinically (ICI), though it was withdrawn at an early stage, prontosil (diaminoazobenzenesulfoname) is a red-coloured sulphonamide with antibacterial activity, converted in vivo to sulphanilamide as active metabolite. It is of historical importance as the first agent of this type (Domagk, 1935). It is also a carbonic anhydrase inhibitor, used experimentally. 

Researchers (Nuijens et al., 1997) at the Leiden University (the Netherlands) in collaboration with Pharming, NV (Leiden, the Netherlands) compared recombinant human lactoferrin (rhLF) expressed in the milk of transgenic mice with natural human milk-derived lactoferrin (hLF). They concluded that the unsaturated rhLF and natural hLF had comparable properties, indicating that hLF produced in bovine milk will exert similar, if not identical, antibacterial and anti-inflammatory activities in vivo. Pharming also developed the first transgenic bull in the late... 

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