Synthesis, of Novel Piperine Analogs of Dipeptidyl Boronic Acid as Antimicrobial and Anticancer Agents

Boronic acids have been illustrious in the literature back in 1860 [1], developing over the years into a wide studied area of chemistry. After the approval of Velcade® as proteasome inhibitor, boronic acids have emerged as a unique lead for several malignant tumors, as β-lactamase inhibitors, NS3 protease inhibitors, amino-acyl tRNA synthase inhibitors, and anticoagulants. Boronic acids and its derivatives have gained outstanding importance as a result of their wide-spread biological activity and their use in synthetic chemistry. Piperine, alkaloid from Piper nigrum L found to display an ample spectrum of pharmacologic activities, together with antimicrobial [2] and antineoplastic properties [3,4]. Despite the acclaimed potential of piperine, up to now there are few reports available for piperine based antimicrobial and antineoplastic agents. Recent development of conjugate molecules between natural products and synthetic molecules emerged as a new approach in the discovery of novel bioactive agents. Piperine amides or piperine ester analogs were potential cytotoxic agents against different neoplastic cell lines than the parent compound piperine. The activity of piperine lies mostly within the amide linkage [5]. Piperine enhances bioavailablity of drugs [6]; this prompted us to synthesize piperine derivatives of dipeptidyl boronic acid. Encouraged from our antecedent research, we wish to further exploit amide linkage of piperine to get a better antineoplastic and antimicrobial agent.