gyrase inhibition
TRANSCRIPT
GYRASE INHIBITION
Presented by,Raghavendra Prabu K S
M.Tech I Year Biopharmaceutical Technology
Topics covered Introduction3 D StructureInhibitors (Drugs)Classification of drugs Mechanism of action DerivativesReferences
Gyrase: DNA gyrase is an essential
bacterial enzyme that catalyzes the ATP-dependent negative super-coiling of double-stranded closed-circular DNA
It belongs to the class Topoisomerase
Topoisomerases are isomerase enzymes that act on the topology of DNA.
Bacterial DNA gyrase is the target of many antibiotics, including nalidixic acid, novobiocin, and ciprofloxacin.
Here the Inhibitors such as Quinolones mainly against Gram negative bacteria
Due to their action on DNA gyrase
While action on Topoisomerase IV on Gram positive bacteria
Structure of DNA GYRASE enzyme in Eukaryote
Gyrase Structure
Inhibitors ~2 main classificationQuinolones ,particularly
fluroquinolones with their broad antimicrobial activity are used in disease causing oraganisms.
Fluroquinolones are the drugs that are chemically related to nalidixic acid and has fluorine in their chemical structure.
QuinolonesThe quinolones are a family of
synthetic broad-spectrum antibiotic drugs.
Quinolones, and derivatives, have also been isolated from natural sources (such as plants, animals and bacteria) and can act as natural antimicrobials and/or signalling molecules.
Quinolones inhibits(a) DNA gyrase ~topoisomerase II(b)DNA topoisomerase IV
Nalidixic Acid 4-quinolone derivaiveEffective against G-ve bacteria __ E.coli ,
shigella , many strains of proteusRelatively ineffective against G+ve
bacteria due to development of resistanceReadily absorbed in GI tractSerum level of the drug usually low80 % eliminated thru, urine span of 8hrs20% active and inactive forms in the urine
Fluroquinolones The fluorine in the chemical
structure called fluoroquinolones Chemically related to nalidixic acid
This fluorine increases the activity of spectrum
Highly effective orallyBactericidal with broad spec
Effective against bacteria which are resistant to beta lactum and aminoglycoside
They are also safe to use
Fluroquinolones Generations
Generation Name Oral bioavl. T half Indications2 Class I Norfloxacin 30 – 40 % 3- 4 hrs UTI,
ProstatitisLomefloxacin 90 % 6 – 8 hrs
2 Class II OfloxacinCiprofloxacin
60-7095
3. 3 to 4.95 to 7
UTI, Typhoid,Gonorrhea,Gastroentiritis, skin ,soft tisue infections
Pefloxacin 90 8-133rd Gen Levofloxacin
SparfloxacinGemifloxacin
>90
70
6-8 Preferred in community acquired Pneumonia
Moxifloxacin 90 7
These Fluroquinolones also effective against Legionella, brucell, chlamydia and mycoplasma pneumoniea
Mycobacterium tuberclosis and M.avium complex
Quinolones such as ciprofloxacin are potent liver enzyme inhibitors and can reduce the metabolism of warfarin, theophilline and sulfonylurease
Therapeutic usesQuinolones..Urinary tract infections, even when
caused
by multifrug-resistant bacteria, intestinal and
biliary tract infections, soft tissue infections,
Respiratory tract infections.
A/EAdverse effects include…GI Toxicity : nausea, diarrhoea
CNS Toxicity: dizziness, headache mildly,
Tendon and cartilage damage : rupture of shoulder, hand, achilles tendons
References :-https://
www.ncbi.nlm.nih.gov/pubmed/1657531
Wikipedia for structurePharmacology and
Pharmacotherapeutics book R.S.Satoskar 24th edition