1,4-Dihydropyridine Scaffold in Medicinal Chemistry, The Story So Far And Perspectives (Part 2): Action in Other Targets and Antitargets

E.      Carosati; P.      Ioan; M.      Micucci; F.      Broccatelli; G.      Cruciani; B.S.      Zhorov; A.      Chiarini; R.      Budriesi

Abstract

1,4-Dihydropyridines were introduced in the last century for the treatment of coronary diseases. Then medicinal chemists decorated the 1,4-DHP nucleus, the most studied scaffold among L-type calcium channel blockers, achieving diverse activities at several receptors, channels and enzymes. We already described (Ioan et al. Curr. Med. Chem. 2011, 18, 4901-4922) the effects of 1,4-DHPs at ion channels and G-protein coupled receptors. In this paper we continue the analysis of the wide range of biological effects exerted by compounds belonging to this chemical class. In particular, focus is given to the ability of 1,4-DHPs to revert multi drug resistance that, after over 20 years of research, continues to be of great interest. We also describe activities on other targets and the action of 1,4-DHPs against several diseases. Finally, we report and review the interaction of 1,4-DHPs with the hERG channel, transporters and phase I metabolizing enzymes. This work is a starting point for further exploration of the 1,4-DHP core activities on targets, off-targets and antitargets.

Keywords: 1, 4-Dihydropyridine, alzheimer disease, anti-atherosclerotic action, antitargets, calcium antagonists, cytochromes P450, glucorticoid hormone receptors, HIV-1 protease inhibitors, MDR, oxidative stress prevention, PAF antagonists, P-gp, TRH, tuberculosis