Why natural products are better drug candidates..?? Part-2

This post is intended to explain the recent developments in natural drug discovery. After careful review of journals I am presenting my views in this blog, hope you enjoy the reading.  In last post we discussed about why research into natural products in pharmaceutical industry has been decreased was discussed. 

Now I would like to discuss furthermore about this issue and what are the factors influencing the improvement in natural products research. Today modern pharmaceutical market is requiring rapid screening and lead identification, in this environment traditional drug discovery involving extract-library screening, bio-assay guided isolation and further development is always negative side. However recent advancements in research encouraged new interest in natural product research.

Here few of the reasons why natural products can be acted as better drug candidates and what advances in technology make it easy to screen the natural compounds from it's libraries. In my previous post I discussed about why research into natural products has been decreased.

(1) Characteristics of chemical diversities:

Feher and schemand examined the combinatorial, natural and synthetic compounds libraries based on their drug-like properties and chemical diversity. Along with their investigations other investigations proved that natural products would consists of more chiral centres and increased stereo complexity in compared with other two libraries.

(2) Natural products are well suitable in modulating protein-protein interactions:

Chemical diversity in natural compounds allows them to bind multiple targets. This additional advantage not only good sign in treatment but also in ‘’HIT’’ selection during drug discovery. We can call this chemical scaffolds embody multiple bindings as privileged structures. This multiple binding capacity used as starting point for establishing screening-design libraries Ex: Yohimbin, Paclitaxel and Vancomycin used solid-phase synthesis of libraries.

This propensity of natural products to binding various targets could useful in therapeutic areas of cancer, immune disorders and signal transduction. These therapeutic areas required a drug candidate with multiple binding properties and which can disrupt the selective protein-protein interactions.

Figure: This figure is about chemical process of natural drug discovery. The first step is extraction of compound in purified form from it's component. Recent technologies like HPLC and LC-MS made this process very fast and less difficulty. After further identification and SAR (structural activities studies ) the production would scale up. The feasibility of it modifying biological response would be further assessed and further optimization by traditional medicinal chemistry would occur. 

(3) Natural products high-throughput screening (HTS):

High-throughput screening: The identification of a drug for it’s activity against a specific target is required testing of large collection of compounds (Libraries). Normally most of the natural products occurs in the form of crude mixture (10-100) compounds and semi-pure mixture (1-10) compounds.

In case of natural products after identifying HITS from their libraries further extraction and biological evaluation is required this is one of the hurdles in identifying ‘’HIT’’ compounds. The second one is natural products mixture at various combinations really challenged the assay robustness in the early days before the advancements in genomics and recombinant DNA technology.

Even though newer molecular biological techniques fasten the drug discovery it added further complex in natural product selection. This is the reason of very big dip in natural product research in last two decades.

But advancements in assay detecting techniques improved natural drug discovery process. Significant success has been achieved in HTS analysis of natural compounds by using Fourier transform ion cyclotron resonance mass spectroscopy (ESI-FTICR) against RNA targets. So these and other advanced technologies make it that future natural product screening need not to be developed only on HTS.

The advanced technologies which increasing interest towards the natural products drug discovery would be discussed in further posts..... Feel free to leave your comments.

Thank you.

With regards,

Santhosh Rao Mennani,

Research Assistant,M.S Pharmacology.

Posted in: My reviews