From the Guidelines
Lincosamides have a unique chemical structure characterized by a pyrrolidine ring linked to a sugar moiety, which allows them to bind to the 50S ribosomal subunit of susceptible bacteria, inhibiting protein synthesis. The core structure of lincosamides includes a methylthiolincosamide moiety attached to a propylproline group, with clindamycin being the most well-known example of this class, as described in the study published in the journal Otolaryngology--head and neck surgery 1. The structure of lincosamides, such as clindamycin, enables them to be effective against many gram-positive bacteria and some anaerobes, including susceptible gram-positive aerobes and anaerobes, as well as many gram-negative anaerobes 1. Some key features of the lincosamide structure include:
- A pyrrolidine ring linked to a galactose sugar through an amide bond
- A methylthiolincosamide moiety attached to a propylproline group
- The ability to bind to the 50S subunit of bacterial ribosomes, inhibiting protein synthesis by interfering with peptidyl transferase activity
- A unique side effect profile, including the potential for gastrointestinal disturbances and, rarely, Clostridioides difficile-associated diarrhea. The presence of the sugar moiety in the lincosamide structure contributes to their ability to penetrate tissues well, particularly bone tissue, making them useful for treating bone and joint infections, although this specific information is not mentioned in the study 1.
From the FDA Drug Label
The chemical name for lincomycin hydrochloride is Methyl 6,8-dideoxy-6-(1-methyl-trans-4-propyl-L-2-pyrolidinecarboxamido)-1-thio-D-erythro-α-D-galacto-octopyranoside monohydrochloride monohydrate. The molecular formula of lincomycin hydrochloride is C18H34N2O6S·HCl·H2O and the molecular weight is 461. 01.
The lincosamide structure is represented by the chemical name and molecular formula of lincomycin hydrochloride, which is Methyl 6,8-dideoxy-6-(1-methyl-trans-4-propyl-L-2-pyrolidinecarboxamido)-1-thio-D-erythro-α-D-galacto-octopyranoside monohydrochloride monohydrate with a molecular formula of C18H34N2O6S·HCl·H2O 2.
- The molecular weight is 461.01.
- The structural formula is mentioned to be represented below in the label, but the actual structure is not provided in the text.
From the Research
Lincosamides Structure
- Lincosamides are a class of antibiotics that exhibit biological activity against bacteria, especially Gram-positive ones, and also protozoans 3.
- The chemical structures of lincosamide antibiotics have been summarized and described, including lincomycin and its semi-synthetic derivative clindamycin 3, 4.
- Lincosamides have a unique structure, including an eight-carbon aminosugar (lincosamide) functionalized with diverse l-proline derivatives and sulfur appendages 4, 5.
- The biosynthesis of lincosamide antibiotics involves an intersection of anabolic and catabolic chemistry, with many reactions that are usually involved in degradation and detoxification playing a constructive role in biosynthetic processes 5.
Key Components
- Lincomycin and clindamycin are widely used in clinical practice as bacteriostatic agents, inhibiting protein synthesis in sensitive bacteria 3, 6.
- The structure of lincosamides includes a trans-4-propyl-l-proline residue, which is formed through an oxidation-associated degradation-like pathway 5.
- Mycothiol (MSH) and ergothioneine (EGT) are small-molecule thiols that play a role in the biosynthesis of lincosamide antibiotics, mediating an eight-carbon aminosugar transfer, activation, and modification 5.
Biosynthesis
- The biosynthesis of lincosamide antibiotics involves a series of complex reactions, including heme peroxidase-catalyzed ortho-hydroxylation and non-heme 2,3-dioxygenase-catalyzed extradiol cleavage for l-tyrosine processing 5.
- The biosynthetic pathways of lincosamide antibiotics also involve thiol-mediated detoxification metabolism, with related intermediates including an MSH S-conjugate, mercapturic acid, and a thiomethyl product 5.