Human ABC transporters such as P-gp and MRP1 contribute to chemotherapy resistance, but small modifications to anthracycline compounds produce compounds such as annamycin with reduced export, leading to substantially improved activity against multidrug-resistant cancer cells [59].
Subsequent modifications to these compounds included elimination of phosphates and changes in the core purine and sugar moiety, resulting in identification of the first selective and stable nonphosphate P2Y12 antagonist AR-C109318XX.
Recent reports have also shown that small structural modifications to related compounds in a series including benzaldazine and (phenethynyl pyrimidine scaffolds can bind to a single allosteric site to exert effects ranging from partial to full antagonism to positive allosteric modulation (18, 28, 29).
These modifications led to compounds with nanomolar-range affinity (e.g. 6a, Ki = 40 nM) and high antagonist activity (e.g. 6a, IC50 = 70.6 nM).
Photochromic properties can be selectively altered by introducing structural modifications to the parent compound, namely, by varying substituents attached to certain positions.
These modifications has led to compounds with promising dual affinity and high MTs receptors agonist activity.
This shows that any major modification to the compound causes a loss in biological activity.
Modifications to our prototypical lead compound TDR32750 have been shown to yield compounds that retain in vitro activity.
Compounds 13e, 13i, 13k, 14a, 14c, 14i, and 14k exhibited significant minimum inhibition concentrations, when compared with first line drugs isoniazid (INH) and rifampicin (RIF) and could be ideally suited for further modifications to obtain more efficacious compounds in the fight against multi-drug resistant tuberculosis.
The types of graphene material and their chemical modifications to produce novel graphene compounds provide different levels of dispersibility and impurities within the nanomaterials.
