Innovations Item Code: IN-2024-2100524
Sector: Health/Telemedicine
Description:
In this work, Quinoline compounds were initially synthesized and characterized, then investigated using webservers (ADMET, Molecular Docking, Bioactivity and Molecular dynamics) for in silico drug likeness against P. Falciparum proteins. The Compound A31, 2-(2-benzoyl-4-methylphenoxy)-8-methyl-6-(trifluoromethyl) quinoline-3-carbaldehyde, showed highest binding energy and, outperformed 15 standard reference antimalarial drugs (atovaquine, mefloquine, Amodiaquine, lumefantherine, artemeter, artesunate etc) although it showed mild carcinogenicity which is similar or better to fourteen of the fifteen antimalarials investigate.
Thereafter, to obtain a better drug like compound, fifty hypothetical derivatives were designed using Chemdraw software from which in silico investigation revealed the higher binding energy and nontoxic target compound (2-(2-benzoyl-4-methylphenoxy)-8-methyl-6-(trifluoromethyl)quinoline-3-carbaldehyde) as a lead antimalarial compound, outperforming the 15 reference antimalarial drugs as a ligand against fifty P. Falciparum parasite proteins.
Interestingly, molecular dynamics study shows the target compound having stable hydrogen bonding and good stability.
Finally, we propose to load the 2-(2-benzoyl-4-methylphenoxy)-8-methyl-6-(trifluoromethyl)quinoline-3-carbaldehyde on a lipid nanocarrier using microemulsion technique to enhance its bioavailability and pharmacokinetic properties while minimizing potential side effects associated with conventional therapies.
This proactive approach is consistent with the design of next-generation antimalarials allowing for targeted drug delivery and sustained release in the body
Stage of Innovation: Proof of Concept (You have created something to show the innovation can work)
Problem:
Virulent strain of plasmodium falciparum is particularly severe and can lead to serious complications, including death if not treated promptly and effectively.
The goal of the project is to prepare a new lead antimalarial compound (2-(2-benzoyl-4-methylphenoxy)-8-methyl-6-(trifluoromethyl)quinoline-3carbaldehyde) with much higher binding energy to amino acids of the parasite proteins leading to greater inhibition and less toxicity at any stage; liver, blood, parasitic stage. The compound should outperforms all the commonly recommended standard reference antimalarial drugs like atovaquine, mefloquine etc.
Unique Selling Point: Most Pharmaceutical companies synthesize large number active compounds and then undertake biological studies to ascertain their efficacy. This approach consumes time and resources. Few companies now undertake computer guided drug discovery. In this design we are deploying the power of computer aided drug discovery and nanotechnology to obtain a lead drug compound with much higher binding energy, less toxicity and outstanding drug likeness. Additionally, we will take advantage of the benefits of the emerging field of nanomedicine using a lipid nanocarrier as vehicles for the controlled delivery of the target compound. Currently, standard antimalarial reference drugs are not delivered through nanocarriers or enhanced through nanotechnology.