Different antimicrobial drugs have different mechanism of actions like on cell wall synthesis, plasma membrane integrity, nucleic acid synthesis, ribosomal function etc. Generally Gram negative cell wall is resistant to many hydrophilic antimicrobial molecules due to high lipid and lipoprotein content, which is comparatively low in Gram positive bacteria. Some receptors of the drug may be present on the bacterial cell, which are involved in the active uptake.

Dear Chintamani Jadhav,

I agree with Mamta Purohit. Indeed, you have different pathways to fight bacteria. For example: sulfanilamide derivatives act on cellular metabolism which block folic acid synthesis essential for coenzyme F synthesis, penicillines act on cell wall (covalent bond), valinomycine acts on plasmic membrane, rifamycines and aminoglycosides act on protein synthesis and DNA intercalants (e.g. quinolones and fluoroquinolones)act on transcription and replication of DNA.

Now, when you have your target you can indeed make a QSAR study. For example, you would like to work on molecules which act on protein synthesis, you select first molecules of interest and then make a quantitative structure activity relationship between their structures and their activities (IC50). By this way you can have a look on functional groups which are essential for activity or can increase the activity of your new design molecules.

Now, for permeability I think it is a little bite difficult to say because you have to take in consideration that when a drug pass through the cell wall, it is "degradated" by beta-lactamase.

I hope that it help you.

Regards

PS: for QSAR study you can use Open3DQsar (free available)

@Enrico open 3DQsar is really nice tool. Thank you very much for sharing.

@Mamta and Enrico, yes i am agree with what you said. However my concern is related to penetration of molecule through bacterial cell.

I will explain in depth, Suppose we perform enzymatic study for TopoisomeraseIV using some quinolone as its inhibitor, and we get activity in nano-molar. When we repeat same study on bacterial cells, we get activity for same molecule in micro-molar range. Further to this we never found correlation between activity on enzymatic assay and on cell line study. Means the molecule which shows excellent activity at enzymatic level may fail at cellular level. The reason behind this is that this molecule have less permeability for bacterial cell wall.

The concern starts from here is that, which factor affect penetration of these molecule through the bacterial cell wall. If we know that factor, it will help for developing antibacterial agent.

If their is any QSAR study reported for bacterial permeability study we can directly use that QSAR equation to predict the permeability of of our newly designed molecule.

And i am looking for such Data or Tool or QSAR article or any scientific article which will help me for above said concern.

Yes permeability can be a problem but you can also see some efflux pump effect. Are your compounds selective towards others enzyme inside bacteria? Indeed for example for pseudomonas aeruginosa there are similar inhibitors (sharing a quinolone or quinoline core) which act on PQS.

@ Enrico.

Actually what ever i explained in previous comment is example basis. I am not asking any thing specifically to that explained examples. we just want to know the thing in general. Further to your query on effux by pump, lets suppose the activity were checked on bacteria having no any efflux pump on it. Our main focus is to know which is most important factors, affecting permeability. I hope you get my concern.

Thanks

Ok. So if you just want to see what parameters affect permeability, you may check for your qsar model lipophilicity/hydrophilicity, charges shared by your compounds (electronic repulsions or attractions) and shapes of your inhibitors (linear vs globular).

Regards

Yes agreed, but i am not getting any appropriate data, which i can directly used for QSAR study. Mostly i am looking for any ready made tool or QSAR performed for permeability study, so that i can directly apply it to my data set. I tried at my level best by using various search strategy to search such tool or any data set or QSAR, but not find relevant thing.

Talking about this and similar topics in my last review article

https://www.tandfonline.com/doi/abs/10.1080/17460441.2018.1455660?journalCode=iedc20

Best regards