Total Synthesis of the Natural Chalcone Lophirone E, Synthetic Studies toward Benzofuran and Indole-Based Analogues, and Investigation of Anti-Leishmanial Activity

• Published in: Molecules (Basel, Switzerland) Switzerland), 2022-01, Vol.27 (2), p.463
• Main Authors: Pozzetti, Luca, Ibba, Roberta, Rossi, Sara, Taglialatela-Scafati, Orazio, Taramelli, Donatella, Basilico, Nicoletta, D'Alessandro, Sarah, Parapini, Silvia, Butini, Stefania, Campiani, Giuseppe, Gemma, Sandra
• Format: Article
• Language: English
• Subjects: 2-arylbenzofuran; 2-arylindole; Antiinfectives and antibacterials; Antiparasitic agents; Antiparasitic Agents - chemistry; Antiparasitic Agents - pharmacology; Antiviral activity; Benzofuran; Benzofurans - chemistry; Biflavonoids - chemical synthesis; Biflavonoids - chemistry; chalcones; Chalcones - chemical synthesis; Chalcones - chemistry; Chemical Phenomena; Chemistry Techniques, Synthetic; Enzymes; Fluorides; Humans; Indoles - chemistry; Inflammation; Investigations; Leishmania infantum; Leishmania spp; Molecular Structure; Natural products; Parasitic diseases; Promastigotes; Structure-Activity Relationship; Ulcers
• ISSN: 1420-3049; 1420-3049
• DOI: 10.3390/molecules27020463

The potential of natural and synthetic chalcones as therapeutic leads against different pathological conditions has been investigated for several years, and this class of compounds emerged as a privileged chemotype due to its interesting anti-inflammatory, antimicrobial, antiviral, and anticancer properties. The objective of our study was to contribute to the investigation of this class of natural products as anti-leishmanial agents. We aimed at investigating the structure-activity relationships of the natural chalcone lophirone E, characterized by the presence of benzofuran B-ring, and analogues on anti-leishmania activity. Here we describe an effective synthetic strategy for the preparation of the natural chalcone lophirone E and its application to the synthesis of a small set of chalcones bearing different substitution patterns at both the A and heterocyclic B rings. The resulting compounds were investigated for their activity against promastigotes disclosing derivatives and , as those endowed with the most interesting activities (IC = 15.3, 27.2, 15.9 μM, respectively). The synthetic approaches here described and the early SAR investigations highlighted the potential of this class of compounds as antiparasitic hits, making this study worthy of further investigation.