Lincomycin, antibacterial activity

Whereas introducing a thiol moiety at C-7 markedly reduced the antibacterial activity relative to lincomycin (79), the 7(3)-7-deoxy-7-alkylthiolincomycins exhibited considerably enhanced antibacterial activity without apparent regard for the size of the alkyl group (80—82). A marked increase in gram-negative activity was shown when the 7(3)-substituent contained a 2- or 3-hydroxy or amino group, but this activity was insufficient to be effective in infected mice (83—85). 

Lincomycins bacteriostatic activity is based on the inhibition of the bacterial proteic synthesis. Lincomycin A in particular have been largely employed in clinical therapy of infections caused by micoplasmas, Gram-positive bacteria, and cocci but it presents a lot of side effects overcome by 7-clindamycin (Fig. 21), a semi-synthetic drug with larger spectrum of action and major antibacterial activity. 

Gindamydn has antibacterial activity similar to that of erythromycin. It exerts a bacteriostatic effect mainly on gram-positive aerobic, as well as on anaerobic pathogens. Gindamycin is a semisynthetic chloro analogue of lin-comycin, which derives from a Streptomyces species. Taken orally, clindamycin is better absorbed than lincomycin, has greater antibacterial efficacy and is thus preferred. Both penetrate well into bone tissue. 

This drug exceeds lincomycin in all positive respects, including absorption into the gastrointestinal tract, antibacterial activity, and antimicrobial spectmm. Synonyms of this drag are cleocin, clinimycin, dalacin, and others. 

Accompanying lincomycin in S. lincolnensis fermentations is a small amount of the analogue 4 -depiopyl-4 -ethyHincomycin, (, 1 I which has considerably lower antibacterial activity than the parent compound. Extension of the normal six-day fermentation to twelve days resulted in the formation of lincomycin sulfoxide, (GrH N-jOvS, and 1-demethylthio 1 hydroxylincomycin (lincomycose), C r,11,> NO, both of which have greatly reduced antibacterial activity. 

Lewis, C. Stern, K.F. Grady, J.E. Comparison in laboratory animals of the antibacterial activity and absorption of lincomycin hexadecylsulfamate to lincomycin hydro- 63. chloride. In Antimicrobial Agricultural Chemotherapy, 1964 ... 

Lincocin lincomycin. lincomycin (ban. inn) (Lincocin ) is an antibiotic produced by Streptomyces lincolnensis and other S. spp. Clinically, it shows broad-spectrum antibacterial activity, lindane (ban. bsi. inn. iso. usan (gamma benzene hexachloride (ban) gamma-BHC Quellada ) is an insecticide. SCABICIDAL and PEDICULICIDAL AGENT. It can be used topically to treat parasitic infestation by mites and lice, linetastine (inn) (TMK 688) is a piperidinylethylpentadienyl derivative, a (5-) lipoxygenase INHIBITOR, an ANTIINFLAMMATORY with inhibitory effects in mouse skin tumour model. 

The in vitro antibacterial activity of members of leucomycin complex increased with increasing partition coefficient and removal of testification of the three hydroxyl of the macrolide ring. The in vitro activity of the NH lincomycin was positively correlated with log partition coefficeint (Optimum > 2.7). Electronic and steric factors also influenced the activity of leucomycin and lincomycin antibiotics (78). 

McGehee RF, Smith CB, Wilcox C, Finland M. Comparative studies of antibacterial activity in vitro and absorption and excretion of lincomycin and cUnimycin. AmJMedSci (1968) 256,... 

The clinically important antibiotic lincomycin [1, 2] exerts its antibacterial activity by the inhibition of protein synthesis at the ribosomal level. A study of the structure of lincomycin by Hoeksema and co-workers [3] employing both classical chemical degradation and nuclear magnetic resonance data, led to the announcement of the structure of the molecule. Lincomycin proved to be a member of a new class of antibiotics characterized by an alkyl 6-amino-6,8-dideoxy-l-thio-D-erythro OL-D-galacto-octopymno- side joined with the proline moiety by an amide linkage (Fig. 1). 

Lincomycin B (4 depropyM -cthyHincomycin) was first reported by Argoudelis et al. (26) in 1965 as a minor component in the fermentation by S. Imcobiensis. Lincomycin B is considered an undesirable sidc product since it possesses only approximately 25% (w/w) of the antibacterial activity of lincomycin A (16). It differs from lincomycin A by having one less methylene carbon in the side chain of the piopylhygric acid moiety (Figure 1). 

Chloro-7-desoxylincomycin (clindeunycin) is well suited for anti-infectious treatment of infants and children . 7-Deoxy-7(R)- and -7 S)-thio-lincomycin possessed slight antibacterial activity . Microbial transformation of clindamycin produced clindamycin sulfoxide which had one fourth of the antibacterial activity of the parent antibiotic against lutea . ... 

The total synthesis of quantamycin [61], necessitated the development of methodology to create a somewhat strained tra j-peihydrofuropyran structure with the required appendages. The adenine moiety was attached by a unique method whereby a bicyclic thioglycoside was treated sequentially with N-benzoyl adenine and bromine [62]. Quantamycin was found to have approximately 8-10% inhibition of binding of lincomycin or erythromycin at the same concentration to ribosomes from Streptomyces. However, no in vitro antibacterial activity was found, which may be an intrinsic problem, or a pharmacodynamic effect due to improper partitioning. 

Erythromycin has much the same spectrum of antibacterial activity as penicillin, and is specially valued for penicillin-sensitive patients. It has almost no side-effects and is well tolerated by children. Because it is acid-labile, it is often prescribed as an insoluble salt (especially the stearate) from which it is liberated in the small intestine, or as an ester (e.g. the propionate). Both erythromycin and lincomycin inhibit the up-... 

Lincomycins are similar to macrolides in biochemical mechanism of action and antibacterial spectrum of activity. They are sulphur-containing antibacterials, first... 

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