Dear fellow researchers,

I have been studying potency of several phytoconstituent of Ayurveda medicinal plants against acetycholinesterase enzyme using a computational approach. I have understood that current Lipinski's rules and other ADME-Toxicity validation criteria doesn't always align well with natural products or natural product derived compounds. Given the higher molecular sizes and masses of most such compounds it seems obvious that none of these compounds should follow prevailing drug-likeness criteria.

My question is does these NP compounds require to follow such criteria for druggability or is there any other set of rules specific NPs?

I have read that, Lipinski Rule of 5 only holds for compounds that are not substrates for active transporters. How does this statement apply for novel drug discovery using natural products?

I appreciate your defense to above argument with possible literature.

Awaiting your kind reply,

Thank you