A Pyridyl-Linked Benzimidazolyl Tautomer Facilitates Prodigious H<sup>+</sup>/Cl<sup>–</sup> Symport through a Cooperative Protonation and Chloride Ion Recognition
Abhishek Mondal, Javid Ahmad Malla, Harshad Paithankar, Shilpy Sharma, Jeetender Chugh, Pinaki Talukdar
Abstract
We report two pyridyl-linked benzimidazolyl hydrazones as HCl cotransporters that are 5 and 2 times superior to prodigiosin, a natural product whose transport efficiency has never been routed by synthetic molecules. These hydrazones provide a suitable HCl binding site through a cooperative protonation and chloride ion recognition. HCl transport by the most active compound induces lysosome deacidification. Viability assays confirmed that the compounds induce cytotoxicity toward human breast cancer MCF-7 cells but are relatively nontoxic toward noncancerous HEK293T cells.
Topics & Concepts
ChemistryProtonationChlorideMoleculeSymporterCytotoxicityTautomerIonStereochemistryCombinatorial chemistryMedicinal chemistryBiochemistryOrganic chemistryTransporterIn vitroGeneMicrobial Metabolism and ApplicationsBiochemical Analysis and Sensing TechniquesAlkaloids: synthesis and pharmacology