Activity–lipophilicity relationship studies on P-gp ligands designed as simplified tariquidar bulky fragments

Design, synthesis, biological evaluation, NMR and DFT studies of structurally simplified trimethoxy benzamides as selective P‐glycoprotein inhibitors: the role of molecular flatness

“…Consequently, it is easy to postulate that high lipophilicity is a key feature for high P‐gp inhibitory activity. This is also supported by the linear correlation between this physicochemical property and the inhibitory activity found for several molecular scaffolds …”

One molecule two goals: A selective P-glycoprotein modulator increases drug transport across gastro-intestinal barrier and recovers doxorubicin toxicity in multidrug resistant cancer cells

“…It has been several years since the authors started dealing with the development of highly potent and selective P-gp ligands, with the aim to hit the undesirable effect due to P-gp mediated efflux of unrelated chemical entities acting as drugs. 12,13,[22][23][24][25][26][27][28][14][15][16][17][18][19][20][21] Starting from our lead compound MC70, bearing a tetrahydroisoquinoline scaffold, displaying high potency vs P-gp 14 , we proceeded in the design and biological evaluation of several series of P-gp compounds identifying compound 1 that emerged as a P-gp ligand able to overcome MDR in cancer stem cells (Chart 1). 25…”

Isoxazole‐Based‐Scaffold Inhibitors Targeting Cyclooxygenases (COXs)

“…THIQ) is as tructuralk ey element of elacridar andt ariquidar (two P-gp saturating substrates or inhibitor-like compounds). [13][14][15][16] Indomethacin, P6, and mofezolac were then linked to either aR h6Go r6 ,7-DM-THIQm oiety to first explore the COX inhibitor recognitiona nd,s econdly, to verify if such new molecules retain P-gp substrate/inhibitor activity.…”