Pharmaceutical and medicinal chemistry Flashcards
What is chemotherapy?
It is the use of drugs to selectively kill infectious cells or invading organisms whithout causing injury to the host.
Examples of organic arsenicals
Suramin and Trypasamide
What is penicillin isolated from ?
Penicillium notatum
Examples of beta lactam antibiotics include?
Penicillins
Cephalosporins
Difference between a bacterial and animal cell
-A bacteria cell has a cell wall and a membrane while an animal cell only has a membrane
- An animal has a nucleus while a bacteria cell has no nucleus
What are the mechanism of antibacterial activity
1) inhibition of antemetabolites
egsulphonamide, they inhibit the enzyme catalysed reactions
2)inhibition of cell wall synthesis-eg penicillin and cephalosporins, this leads to bursting or the cell and death
3)inhibition of protein synthesis eg aminogycosides ,tetracyclines
Disruption of protein synthesis eg aminoglycosides and tetracycline, the essential enzymes for cell growth can no longer be synthesized
Inhibition of nucleic acid, replication and transcription-eg quinolones , they stop cell division
What is the Moa of sulphonamide
They act as competitive enzyme inhibitors and block the biosynthesis of folic acid in bacterial cell.
Sulphonamide has a similar structure to paba which allows it to mimic and bind to dihydrofolate preventing it from producing folic acid.
What is the common side effect of sulphonamide
Steven Johnson syndrome
Eg of sulphonamide
Sufadiazine-it’s zinc and silver salts are used to treat burns and wounds
Quinolones
-used as antimalarial agents
-they inhibit synthesis of bacterial dna by interfering with the action of dna gyrase and topoisomerase 2 or 4
What are antibiotics
They are anti infective chemical substances derived from natural sources to kill or stop the activity of bacteria in the host cell
Classification of antibiotics
Can be classified based on
Biogenetic precursors eg amino acid,sugar polypeptide
Moa eg inhibition of cell wall synthesis, protein,nucleic acid,injury to plasma membrane and essential metabolites synthesis inhibitors
Chemical basis eg beta lactam antibiotics,non lactam,unclassified
Examples of beta lactam antibiotics
Penicillins
Cephalosporins
Clavunalic acids
Monobactam
Carbapenams
Penam
Examples of non lactam
Tetracyclines
Aminoglycosides
Polypeptides
Macrolides
Polyene
Examples of non classified
Chloramphenicol
Fusidic acid
Novobiocin
Beta lactam ring contains how many cyclic amides
4 membered cyclic amide
Alpha lactam
3 rings
Gamma lactam
5 rings
Structure of penicillin
It contain a highly strained 4-membered β -lactam ring fused to a 5-membered thiazolidine ring
Characteristics of penicillin’s
They are not lipid soluble so do not crossthe blood Brain barrier
They are excreted and unchanged by the kidneys
solubility and other physical properties are affected by the acyl side chains
How many chiral centers are in penicillin
3
Cephalosporins
Four-membered ring (3-lactam ring) fused
to a six-membered dihydrothiazine ring
Cephalosporins are considered broad
spectrum antibiotic with high potency against gram negative organism
Clavulanic acid
Clavulanic acid is a β-lactam antibiotic produced by Streptomyces clavuligerus.
It is the first clinically used inhibitor
Monobactams
They are monocyclic β-lactam produced by bacteria.
Eg Azthreonam/Tigemonam
Aminoglycosides
Antibiotics that contain amino sugars
Eg gentamicin ,neomycin,amicasin,tobramycin
-they synergize with beta lactam antibiotics because it incraeses their ability to permeate
Side effects of aminoglycosides include
Can cause permanent damage to 8th cranial nerve causing ototoxicity and nephrotoxicity.
Moa of aminoglycosides
The aminoglycosides irreversibly bind to the 16S ribosomal RNA & freeze the 30S initiation complex (30S-mRNA-tRNA) so that no further initiation can occur.
What are macrolides
-They are chemical related antibiotics from actonomycetes.
-has one or two sugars glycodically linked to the lactine ring
-active against penicllin resistant strains and gram negative bacteria
Eg of macrolides
Erythromycin, Oleandomycin, Carbomycin, Spiramycin, Picromycin
Tetracyclines
They are effective group of antibiotic isolated from Streptomyces species by fermentation.
-has 3 structural features;Tricarbonyl methane, phenolic b-diketone,Dimethylamino group.
Polyenes
They are antibiotics produced by various strains of Streptomyces.
-characterized by a alarge lactone function and a sequnece of of conjugated double bonds.
-active against yeast and fungi but inactive against bacteria
-the more conjugated bond, the greater the antifungal activity.
Eg of polyenes
Amphotericin B, Candicin, Nystatin And Natamycin
how many rings are in Alpha and Gamma lactams?
3 and 5 rings
6-APA means
6–aminopenicillanic acid and is obtained by deacylation of phenoxymethyl penicillin
C atom with the COOH(C-3) has what type of configuration?
Dextro
Amidic C-6 has what type of configuration?
Laevo
properties of penicillins include
the free acids have poor oral and parental absorption
they are poorly lipid soluble and do not cross the BBB
what are Depot preparations?
They are salt repository preparations which are sparingly soluble in water.
they are injected into the muscles and the active substances are slowly released into the blood.
Both Peniciliins and Cephalosporins belong to which precursors?
Cysteine and Valine
what bacteria are 1st Gen cephalosporins more active against?
-they are more active against Gram positive with limited activity against Gram negative
1st Gen Cephalosporins
-eg include Cephalexin, Cephradine,Cefadroxil
-they are hydrolysed by beta lactamase and have lower activity
-they have a single methyl at position C-3 and alpha amino group at C-7 with a phenyl group
2nd Gen Cephalosporins
-Loracarbef has a tetrahydropyrimidine ring because of the C atom in the ring instead of sulphur
eg include Cefuroxime, Loracarbef,Cefotiam
-Cefotiam has an aminothiazole ring at C-3 side chain
3rd Gen Cephalosporins
majority of them have an aminothiazole ring at position C-7
-they are hydrolysed by esterases in the GIT
4th Gen
they have greater activity against gram negative
-they hav C-7 side chain
-they possess a positively charged quarternary nitrogen at C-3 side which makes them easy to diffuse through gram negative bacteria membrane
eg cefozopran
Clavulanic acid(Sulbactam) is produced by?
streptomyces clavuligerus
it is the clinically useful irreversible inhibitor of beta lactamase and is termed as a suicide inhibitor because it gets destroyed in the process.
what does streptomycin comprise of?
streptidine,streptose and N-methyl 1-L-glucosamide
what is the use of neomycin?
for decomtamination of the GIT
Component of Azithromycin
is a semi synthetic erythromycin with rimg enlargement by introduction of N-CH3 btw C9 and C10.
Oleandomycin
-14 atom ring
-contains exocyclic methylene epoxide on C-8
Polypeptide antibiotics
-obtained from genus bacillus
-members include-Bactricin A, polymixin B,Gramicidin.
-has renal toxicity
used topically for burns and skin infections
-acts by inhibing mucopolypeptide cell wall synthesis and interfere with permeability of the cell membrane
what is the indication of chloramphenicol?
-ususlaly for bacterial meningitis
moa of chloramphenicol
they inhibit bacterial protein synthesis caused by Haemophilus influenzae or Neisseria meningitis
when was Isoniazid discovered?
1952, used in the treatment of tuberculosis
4-aminosalicyclic acid
-is a white to yellowish crystalline solid
-has an aq PH 3.2
-the acid undergoes decarboxylation when heated.
Ethambutol
-dextro isomer is 16 times as active as the meso isomer
-only recommended to be used in combination with other antitubercular agent
-it is a white crystalline powder freely soluble in water and alcohol
Rifampicin
-an inhibitor of DNA dependent RNA polymerase
examples of naturally occuring antimalarials include
Quinine-from cinchona officinalis
artemsinine-Artemisia annda
,cinchonine
SAR of Quinine
-oxidation of vinly group to carboxyl-loss of activity
esterification of carboxyl group-restores activity
demythlation of quinine with HBr/AcOH or BCl3 in CH2Cl2-reduced activity
SAR of Artemisinine
-presense of H at C1 and C7-essential for activity
-substitution at C2 and C3-loss of activity
-presense of methyl group at C4-increased antimalarial activity
members of 4 amino quinolones
chloroquine,sontoquine,amodiaquine
