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Methacycline

Methacycline is a tetracycline antibiotic used as a precursor in the industrial synthesis of doxycycline hyclate. It is a broad-spectrum semisynthetic tetracycline excreted more slowly and maintaining effective blood levels for a more extended period than other member of this class. It is active against most Gram-positive bacteria (pneumococci, streptococci, staphylococci) and Gram-negative bacteria (E. coli, salmonella, shigella, etc.), and towards agents causing onithosis, psittacosis, trachoma, and some Protozoa. Like other tetracyclines, the general usefulness of methacycline has been reduced with the onset of bacterial resistance.

Therapeutic use

For the treatment of acute bacterial exacerbations of chronic bronchitis.

Dosage and Administration

 

Toxicology

Organism Test Type Route Reported Dose (Normalized Dose) Effect Source
rat LD50 intraperitoneal 660mg/kg (660mg/kg)   Toxicology and Applied Pharmacology. Vol. 18, Pg. 185, 1971.
 

 

Pharmacokinetic

Bioavailability 58%
Metabolism  
Cmax (mg/ml) 2-3
tmax (hrs) 3
Half-life 14 hrs
Eliminiation rate Constant  
Excretion urinary (33%)
Protein binding 75-78%

Absorption

 

Distribution

 

Elimination

 

Metabolism

 

Mechanism of action

Methacycline, a tetracycline antibiotic, is a protein synthesis inhibitors, inhibiting the binding of aminoacyl-tRNA to the mRNA-ribosome complex. Methacycline inhibits cell growth by inhibiting translation. It binds to the 16S part of the 30S ribosomal subunit and prevents the amino-acyl tRNA from binding to the A site of the ribosome. The binding is reversible in nature. Tetracyclines also have been found to inhibit matrix metalloproteinases. This mechanism does not add to their antibiotic effects, but has led to extensive research on chemically modified tetracyclines or CMTs (like incyclinide) for the treatmet of rosacea, acne, and various types of neoplasms.

 


Medicinal Chemistry

CAS number: 914-00-1  EINECS: 213-017-5

Molecular Formula: C22H22N2O8

Average mass: 442.4187 Da

Monoisotopic mass:  442.13761569 Da

Systematic name: (2Z,4S,4aR,5S,5aR,12aS)-2-[amino(hydroxy)methylene]-4-(dimethylamino)-5,10,11,12a-tetrahydroxy-6-methylene-4a,5a,6,12a-tetrahydrotetracene-1,3,12(2H,4H,5H)-trione

SMILES: [C@@H]12[C@](C(=C3[C@H]([C@@H]2O)C(=C)c2c(C3=O)c(ccc2)O)O)(C(=O)C(=C([C@H]1N(C)C)O)C(=O)N)O

Std. InChI: 1S/C22H22N2O8/c1-7-8-5-4-6-9(25)11(8)16(26)12-10(7)17(27)14-15(24(2)3)18(28)13(21(23)31)20(30)22(14,32)19(12)29/h4-6,10,14-15,17,25,27-29,32H,1H2,2-3H3,(H2,23,31)/t10-,14-,15+,17+,22+/m1/s1

ACD/LogP: 1.347 # of Rule of 5 Violations: 2
ACD/LogD (pH 5.5): -1.18 ACD/LogD (pH 7.4): -1.56
ACD/BCF (pH 5.5): 1.00 ACD/BCF (pH 7.4): 1.00
ACD/KOC (pH 5.5): 1.00 ACD/KOC (pH 7.4): 1.00
#H bond acceptors: 10 #H bond donors: 7
#Freely Rotating Bonds: 7 Polar Surface Area: 181.62 2
Index of Refraction: 1.753 Molar Refractivity: 108.598 cm3
Molar Volume: 265.645 cm3 Polarizability: 43.051 10-24cm3
Surface Tension: 101.496002197266 dyne/cm Density: 1.665 g/cm3
Flash Point: 441.572 C Enthalpy of Vaporization: 122.951 kJ/mol
Boiling Point: 806.527 C at 760 mmHg Vapour Pressure: 0 mmHg at 25C

 


Water solubility: 7550 mg/l (at 21 C)

logP = -0.3

 

 

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