Flavonoids as Inspiration for the Design and Synthesis of New Antiproliferative, Antiparasitic and Antiviral Compounds: An Account

Modified flavonoids of the sub-group of pterocarpans, 5-carba-pterocarpans, 5-carbapterocarpens, 1-carba-isoflavanones, coumestans, and aurones were synthesized and evaluated as antiproliferative, antileishmanial and antiviral. A new scaffold, called pterocarpanquinone, was discovered and LQB-118, the prototypical scaffold of its series, showed consistent antileishmanial (mice and hamster in vivo) and antineoplastic (respectively, human and mice tumors ex vivo and in vivo) activity. 5-Carpa-pterocarpan LQB-485 is potent towards SF-295 cancer cells (CNS). LQB-262 and LQB-34 are new inhibitors of NB5S RdRp polymerase of hepatitis C virus (HCV) while LQB-314 and LQB-360 demonstrated potent activity and selectivity against HCV replicon reporter cells. LQB-454 and LQB-501 were evaluated for their in vitro anti-proliferative effects against human breast cancer and leukemia cell lines with diverse profiles of drug resistance. In breast cancer they present higher toxicity on multidrug resistant cells (collateral sensitivity). Aurone LQB-814, featuring a “lipophilic phenol” at A-ring”, was a very potent and selective inhibitor of SARS-CoV-2 in Calu-3 cells. Other four aurones bearing EC50 (concentration required to inhibit 50% of cell growth) < 1 were also discovered.