Tetrahydroacridinone Scaffold Tuning for Soluble Antimalarials
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Solution Overview
Problem
Current antimalarial drugs face resistance issues and lack aqueous solubility, which is crucial for oral delivery, limiting their effectiveness against Plasmodium spp. parasites.
Innovation Solution
Development of tetrahydroacridin-9(10H)-ones (THAs) with specific substituents that enhance antimalarial activity against multiple parasite stages and improve solubility.
Engineering Contradictions & Design Principles
Engineering Contradiction Analysis
1Reliability
If current antimalarial drugs are used, then treatment effectiveness is maintained, but resistance development occurs and aqueous solubility is insufficient
Solution Approach 1:
The patent modifies the chemical structure of THA compounds by changing parameters such as substituting hydrogen atoms with halogens (fluorine, chlorine, bromine, iodine) at specific positions on the acridinone ring system. These parameter changes in molecular structure improve aqueous solubility while maintaining antimalarial activity against resistant strains, directly addressing the contradiction between effectiveness and solubility/resistance issues
Solution Approach 2:
The invention creates composite molecular structures by combining the tetrahydroacridin-9(10H)-one core scaffold with various substituent groups (halogens, alkyl groups, alkoxy groups, aryl groups, heteroaryl groups) to generate a series of derivative compounds. This composite approach allows optimization of both antimalarial activity and aqueous solubility properties simultaneously
2Reliability
If THA compounds are used, then antimalarial activity against resistant strains is achieved, but aqueous solubility is insufficient for oral delivery
Solution Approach 1:
The patent systematically varies molecular parameters of THA compounds by introducing different halogen substituents (F, Cl, Br, I) at positions 1, 6, and 11 of the acridinone ring, and modifying positions 2 and 7 with various groups. These parameter changes are specifically designed to enhance aqueous solubility to levels suitable for oral formulation and delivery while preserving potent activity against multidrug-resistant Plasmodium falciparum strains
Data Source
AI summary
In accordance with the purpose(s) of the present disclosure, as embodied and broadly described herein, the disclosure, in one aspect, relates to scaffold molecules that exhibit potent antimalarial activity against multiple strains of Plasmodium spp. in the parasite's various stages, such as, for example, the erythrocytic and exoerythrocytic stages, and pharmaceutical compositions comprising same. In one aspect, the compounds are tetrahydroacridinones having the structure I described herein. In another aspect, the compounds described herein can be used to treat or prevent malaria in a subject.