The video explains the Medicinal Chemistry aspects of Aminoglycosides.
Hello everyone welcome to the video on aminoglycosides medicinal chemistry aspects in this video i am going to explain about streptomycin cannabis and neomycin and their mechanism of action structure structure activity relationship and clinical uses this is my youtube channel just type in my name j saradesh you will get the way all the videos if you like the video do
Subscribe and share let’s get into the topic see amino glycosides as the name indicates they have a glycosidic bond amino rings attached to sugars with a glycosidic bond hence chemically they are called as aminoglycosides now mechanism fraction when you see they are called as protein synthesis inhibitor they inhibit protein synthesis in bacteria in bacteria there
Are 50s ribosomal unit and 30s ribosomal unit between that mrna you will get inserted and with the help of trna protein synthesis will happen now what happens with this aminoglycosides is they irreversibly bind to 30’s ribosomal unit 30 years ribosomal unit they will bind and they reduce the amount of proteins being synthesized and they cause errors in amino acid
Sequence and both of them will cause the depth of amino death of bacteria now understand this one usually the protein synthesis inhibitors are bacterial static in nature but aminoglycosides can also cause death hence they are considered as bacteriocyte so they have both both of the features they can work as bacteriostatic by stopping bacteria from multiplying they
Can also act as bactericidal by killing them now one more important feature is they have strong post antibiotic effect that means they remain effective even hours after the levels of antibiotic dropped below minimum inhibitory concentration when the antibiotic concentration is fallen below the minimum inhibitory concentration still they show their actions that is
What is called as post antibiotic effect moving further so you have a lot of aminoglycosides derivatives are there like amicus and gentamicin neomycin streptomycin topromycin streptomycin is specifically used to treat tb mycobacterium tuberculosis and tobromycin is topically used to treat eye infection as well as the nibilized form is used to treat pseudomonas
Originism in people with cystic fibrosis in this way the adverse effects are very much minimized and they are used to treat variety of infections like respiratory tract infection urinary tract blood bone soft tissue infections now see these amino glycosides are specifically effective against aerobic gram negative organisms the reason is in presence of oxygen
Aminoglycosides will get into the bacterial cell see unless they get into the bacterial cell they cannot inhibit protein synthesis and they need oxygen to get inside the bacterial cell they are ineffective against anaerobes where bacteria which do not use oxygen so they can be used to treat protease esterasia called eclipsial infection causing bacteria now
Streptomycin is isolated from a soil bacteria streptomyces gracias in 1944 by salman walkman and walkman is the first researcher who coined the term antibiotic now it was the first effective reason to treat tuberculosis now see it used to be a combination of streptomycin isoniazid and paramanusalic acid but before that the first known antibiotic to use to treat
Tuberculosis was streptomycin now it is also used to treat endoca endococcal endocarditis like that and its activity is more in gram negative than gram positive now the problem is a resistance is rapidly developed that is the reason why it is not recommended as a monotherapy as a single drug streptomycin is never used because of the rapid emergence of resistance
And it is not absorbed orally and it is acid sensitive see when you see the streptomycin it has got a guanido groups guanido groups are strongly basic groups so they develop a positive charge so they cannot be absorbed orally and they are water soluble and see because they are already polar compounds they should be given in intravenous form and metabolism they
Will not be metabolized much they are excreted as such because they are already water soluble now let us see the structure of streptomycin see as we have seen you have a sugar attached to this amino ring with the help of a glycosidic bond hence they are called as amino glycosides now when you see streptomycin is made up of three rings streptadine streptos and
N-methylglucosamine now streptadine is a derivative of inositol in inositol ring at one and three position two guanido groups are attached so it is a derivative of inositol ring which is glycosidically say this is the glycoside bond bound to streptos streptos is a furanose derivative furanos carbohydrate and the streptos is again bonded to n-methylglucosamine
Glucosamine is a pyranose derivative so streptomycin has got all the three rings now when you see the structural activity relationship let us understand these things now see in streptos you have this aldehyde group is there you reduce this aldehyde to alcohol or you oxidize this aldehyde to acids both of them see the problem with reduction of alcohol is it
It creates a it creates dihydrostreptomycin which has got a major adverse effect called severe deafness so reduction will retains the activity but address effect is increased oxidation reduces the activity so there is no point in changing this group now the next one oxidation of methyl group in alpha streptos to methylene hydroxy gives an active analog with
No advantage over streptomycin so this methyl group also give a second methyl group in alpha streptos see this methyl group even if you change it there is no much advantages there now the other things modification of amino methyl group in glucosamine now see in glucosamine there is an amino methyl group is there modifying demethylation you change anything it
Reduces activity of streptomycin now even if there is a change in guanado groups it also decreases activity so all the three rings in streptos you change this aldehyde group to you reduce or oxidize if you reduce it the activity is remained but adverse effects are increased oxidation reduces activity even there if there is a change in methyl group also reduces
Activity glucosamine and methylamine if you change anything it reduces activity gonorrhoea groups are also required for activity so this is about structure activity relationship of streptomycin now the next one is cannamycin now can a myosin is isolated from streptomyces cannabis it is and it is a mixture of at least three compounds a b c now cannabis in gentamicin
Neomycin parameters and all of them are chemically stable now when you see the structure of cannabis in see this c3 hydroxy group is phosphorylated whereas c6 amine is acetylated this is the major pathway of resistance or metabolism by the enzymes if bacteria stimulates this amine group or phosphorylate this hydroxyl group the activity is reduced and that is what
Is a resistance pathway so pseudomonas aeruginosa and end robes are resistant to these drugs you cannot use cannabis and to treat them but it is used in combination to treat mycobacterial diseases now see the cannabis and do not have d ribose molecule that is present in streptomycin kind of flux you can see you don’t have this five-membered ring ribose ring is
Not there all are six-membered rings and all the three differ in this two groups see there is a difference in this t groups remaining everything is similar one moving to the next one now neomycin neomycin is isolated from streptomyces friday as a mixture of abc now it composed of four rings unlike streptomycin and amycin it is composed of four rings and it has
Got less toxic less toxic than streptomycin now it is formulated as a sulfate salt which is hydroscopic photosensitive powder it is mostly used to treat gastrointestinal dermal and peritoneal infection it is a broad spectrum as uh streptomycin the advantage is it is less toxic than streptomycin bacterial resistant is also rarely acquired these two features will
Make neomycin clinical utility more now aminoglycosides let us understand adverse effects of amino glycosides now amino glycosides are auto toxic they damage cochlea and hair cells and that results in hearing impairment if it is enhanced if a person is taking loop diuretics see loop diuretics also cause auto toxicity hearing impairment so the combination of the
These two trucks will enhance that adverse effect nephrotoxic they will cause kidney damage and inhibit the release of acetylcholine and this release when still colon release is inhibited it affects the skeletal muscles and may cause a kind of neuromuscular junction block it is so see neuromuscular junction problems are there in myasthenia gravity so these drugs
Are contraindicated in in people suffering with mysterious gravis some of the non specific adverse effects it may cause nausea vomiting and allergic reactions and it has also shown teratogenic effects so hence they are contraindicated in pregnant women so this is about monoglycosis thank you for watching this video if you like the video do subscribe and share thank you for watching
Transcribed from video
Aminoglycosides – Structure, SAR, Mechanism & Uses of Streptomycin, Kanamycin & Neomycin By G Sai Rajesh
