Clindamycin, structure

Macrolides e.g. erythromycin. Clindamycin, structurally a lincosamide, has a similar action and overlapping antibacterial activity. 

Clindamycin, structurally a lincosamide rather than a macrolide, binds to bacterial ribosomes to... 

Ribosomal Protein Synthesis Inhibitors. Figure 5 Nucleotides at the binding sites of chloramphenicol, erythromycin and clindamycin at the peptidyl transferase center. The nucleotides that are within 4.4 A of the antibiotics chloramphenicol, erythromycin and clindamycin in 50S-antibiotic complexes are indicated with the letters C, E, and L, respectively, on the secondary structure of the peptidyl transferase loop region of 23S rRNA (the sequence shown is that of E. coll). The sites of drug resistance in one or more peptidyl transferase antibiotics due to base changes (solid circles) and lack of modification (solid square) are indicated. Nucleotides that display altered chemical reactivity in the presence of one or more peptidyl transferase antibiotics are boxed. 

Systemic therapy with a variety of (3-lactams, macro-lides and lincosamides (clindamycin) has been the cornerstone of skin infection therapy for many years [17]. However, topical antibiotics can play an important role in both treatment and prevention of many primary cutaneous bacterial infections commonly seen in the dermatological practice [18], Indeed, while systemic antimicrobials are needed in the complicated infections of skin and skin structure, the milder forms can be successfully treated with topical therapy alone [18], The topical agents used most often in the treatment of superficial cutaneous bacterial infections are tetracyclines, mupirocin, bacitracin, polymyxin B, and neomycin. 

In traditional electrophoresis, separation efficiency is limited by thermal diffusion and convection. Owing to long analysis times and low efficiencies, these procedures never enjoyed wide usage. Problems have arisen when trying to differentiate between structurally related drug residues such as streptomycin and dihydrostreptomycin, tetracyclines, lincomycin and clindamycin, and erythromycin and oleandomycin (83, 84). To overcome these problems, anticonvective media, such as polyacrylamide or agarose gels, have also been used. 

Lincomycin. The lincomycins and celesticetins are a small family of antibiotics that have carbuliydrate-lype structures. Clindamycin, a chemical modification of lincomvcin, is clinically superior, Antibiotics in this family inhibit gram-positive aerobic and anaerobic bacteria by interfering with protein biosynthesis. 

H). C,8H34N206S. the first lincosaminide antibiotic to which a structure was assigned, is defined chemically as methyl 6,8-dideoxy-6-(l-methyl-fro/M-4-propyl-L-pyrrolidin-2-ylcarbonylamino)-l-thio-D-erythro-L>-gal-actu-octopyranoside. Both lincomycin and the semisynthetic clindamycin (I, R = H, R = Cl), CisH ClNjOsS, are widely used in clinical practice. The trivial name of the sugar fragment of this antibiotic, methyl a-thiolincosaminide, has lent itself to the other members of this family, whether produced as secondary metabolites of soil microorganisms or derived semisynthetically by chemical modification. 

Clindamycin is a chlorine-substituted derivative of lincomycin, an antibiotic that is elaborated by Streptomyces lincolnensis. Lincomycin, although structurally distinct, resembles erythromycin in activity, but it is toxic and no longer used. 

R, D. Birkenmeyer and F. Kagan, Lincomycin. XI. Synthesis and structure of clindamycin, a potent antibacterial agent, J. Med. Chem. 13 616 (1970). 

Metronidazole and clindamycin are protein synthesis inhibitors that inhibit bacteria by interacting with the DNA to cause a loss of helical DNA structure and strand break-... 

Bndamydn Phosphate, USP. Clindamycin phos-I phate (Cleocin Phosphate) is the 2-phosphate ester of clinda-myviii. It exists as a zwittcrionic structure that is very soluble in water. It is intended for parenteral (intravenous or intramuscular) administration for the treatment of serious infec-iious and instances when oral administration is not feasible. Solutions of clindamycin phosphate are stable at room tem-pnatute for 16 days and for up to 32 days when refrigerated. 

Figure 4 Exemplar structures of various antibiotic classes that bind to either the 505 or the 305 subunit. Macrolides azithromycin (1), oxazolidinones linezolid (2), aminoglycosides Kanamycin A (3), Pleuromutilin (4), phenylpropanoids chloramphenicol (5), lincosamides clindamycin (6), Sparsomycin (7), Anisomycin (8), and tetracycline (9). See Scheme 9 for thiosptrepton (38). Not pictured streptogramins such as quinupristin/dalfopristin.

The structures of two new pyrrolidine alkaloids, pandamarilactonine-A and -B isolated from Pandanus amaryllifolius Roxb, have been deduced by Takayama and co-workers with the help of vicinal Jhc and /hh couplings. Girault and co-workers have determined conformations of free and ribosome-bound macrolide antibiotics using NMR and molecular modelling. The authors analysed Vhc and /hh couplings of the proline and sugar part of lincomydn and clindamycin and of the macrocycle as well as desosamine part of HMR 3647 (telithromycin). ... 

For infected bite wounds, penicillin and a peniciUinase-resistant penicillin or amoxiciUin-clavulanic acid 875 mg/125 mg oraUy twice daily (40 mg/kg per day oraUy of the amoxicillin component divided into two doses) should be started empirically pending the culture results. Tetracyclines or a combination of clindamycin plus a fluoroquinolone or trimethoprim-sulfamethoxazole may be used as an alternative therapy for the penicillin-allergic patient. Hospitalization for minor wounds is not necessary if surgical repair of vital structures has not been performed. Patients suffering serious injuries or clenched-fist injuries should be started on intravenous antibiotics. Duration of therapy for infected bite injuries should be 7 to 14 days. 

Similar structure activity relationships were found in the 4,-alkyl analogues of clindamycin (87). The de - A- me thdclindamycin intermediates including de- /V-methylclindamycin itself, but unlike de- IV-methyllincomycin, are also highly active antibacterially. In addition, they are active in vivo as antimalarial agents (66—68). 

Clindamycin binds exclusively to the 50S subunit of bacterial ribosomes and suppresses protein synthesis. Although clindamycin, erythromycin, and chloramphenicol are not structurally related, they act at sites in close proximity, and binding by one of these antibiotics to the ribosome may inhibit the interaction of the others. There are no clinical indications for the concurrent use of these antibiotics. Macrolide resistance due to ribosomal methylation by encoded enzymes also may produce resistance to clindamycin. However, because cUndamycin does not induce the methylase, there is cross-resistance only if the enzyme is produced con-stitutively. Clindamycin is not a substrate for macrolide efflux pumps thus, strains that are resistant to macrolides by this mechanism are susceptible to clindamycin. Altered metabolism occasionally causes clindamycin resistance. 

These findings are interpreted to indicate that erythromycin resistance mutation in domain II caused an increase in the peptide and disrupted an indirectly functional interaction between domains II and V, because such a mutation could affect alteration of the stability of a secondary rRNA structure (hairpin sequence structure) in domain II. In addition, the Shine-Dalgamo (SD) sequence of the rRNA-encoded E-peptide ORE is sequestered in the hairpin structure. Thereby, SD and E-peptide codon are not accessible to ribosomes of wild-type E. coli. The conformational change of the hairpin structure by erythromycin resistance mutation can be recognized by ribosomes for the initiation of translation of E-peptide. Thus, the increase of the peptide is expected to show resistance to macrolide antibiotics such as erythromycin, oleandomycin, and spiramycin but not clindamycin and chloramphenicol without preventing their binding to the target. 

Methyl penta-A,0-acetyl-a-D-lincosaminide, related to lincomycin (55, X=OH), has been prepared from myo-inosotol/ Lincomycin has been converted by a double inversion sequence via the chloride (clindamycin) into the analogues 55, X=N3, imidazol-2-thiyl, etc/ and the lincosamine-related structure 56 has been made from l,2 3,4-diO-isopropylidene-D-galactose/ ... 

Fig. 6.9 Structures of the naturally occurring antibiotic Uncomycin, which contains the sulfur-containing sugar methylthiolincosamide, and the closely related clindamycin in which the 7-hydroxy substituent is replaced by a chlorine atom...

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