Discovery of bipyridine amide derivatives targeting pRXRα-PLK1 interaction for anticancer therapy

A Unique Hybridization Route to Access Hydrazylnaphthalimidols as Novel Structural Scaffolds of Multitargeting Broad-Spectrum Antifungal Candidates

“…(1) The naphthalimido moiety with a polycyclic aromatic skeleton containing two amido groups is different from the classical antifungal structure; this unique naphthalimido fragment as an antifungal skeletal structure exhibits multitargeting potential with biological targets via noncovalent bonding, which can overcome the globally increasing drug resistance. 17,18 (2) The two carbonyl groups in the naphthalimido backbone may form noncovalent bonds 19,20 with biological targets, 21,22 which are beneficial for enhancing affinity toward targets and regulating physicochemical properties of the designed molecules. (3) A hydroxyethyl moiety is well recognized as a beneficial group in antimicrobial agents, such as fluconazole, in which the hydroxyethyl group can undergo supramolecular interactions with the biotarget molecules via hydrogen bonding as well as improve water solubility and bioavailability.…”

“…Additionally, a prevalent hybridization strategy was employed for designing our target antifungal molecules because molecular hybridization of different fragments from various biologically active compounds into a new single chemical entity could afford unique chemical structures with desired properties. This has been recognized as an effective approach to modulate multiple targets and overcome the serious drug resistance observed worldwide. , Our target molecular structures were chemically designed based on the following factors: The naphthalimido moiety with a polycyclic aromatic skeleton containing two amido groups is different from the classical antifungal structure; this unique naphthalimido fragment as an antifungal skeletal structure exhibits multitargeting potential with biological targets via noncovalent bonding, which can overcome the globally increasing drug resistance. , The two carbonyl groups in the naphthalimido backbone may form noncovalent bonds , with biological targets, , which are beneficial for enhancing affinity toward targets and regulating physicochemical properties of the designed molecules. A hydroxyethyl moiety is well recognized as a beneficial group in antimicrobial agents, such as fluconazole, in which the hydroxyethyl group can undergo supramolecular interactions with the biotarget molecules via hydrogen bonding as well as improve water solubility and bioavailability . Therefore, a hydroxyethyl fragment was inserted into the target compounds.…”

“…The two carbonyl groups in the naphthalimido backbone may form noncovalent bonds , with biological targets, , which are beneficial for enhancing affinity toward targets and regulating physicochemical properties of the designed molecules.…”