Synthesis, cytotoxic and antioxidant evaluations of amino derivatives from perezone

• Published in: Bioorganic & medicinal chemistry Vol. 20; no. 17; pp. 5077 - 5084
• Main Authors: Concepción Lozada, M., Soria-Arteche, Olivia, Teresa Ramírez Apan, Ma, Nieto-Camacho, Antonio, Enríquez, Raúl G., Izquierdo, Teresa, Jiménez-Corona, Arturo
• Format: Journal Article
• Language: English
• Published: Amsterdam Elsevier Ltd 01-09-2012; Elsevier
• Subjects: alpha-tocopherol; amines; Amino acids; Amino derivatives; Animals; Antineoplastic Agents - chemical synthesis; Antineoplastic Agents - chemistry; Antineoplastic Agents - pharmacology; antioxidant activity; Antioxidants; Antioxidants - chemical synthesis; Antioxidants - chemistry; Antioxidants - pharmacology; Biological and medical sciences; Brain - drug effects; Brain - metabolism; Cell Line, Tumor; Cell Proliferation - drug effects; Cell Survival - drug effects; Cytotoxic; Cytotoxicity; Data processing; Dose-Response Relationship, Drug; Drug Screening Assays, Antitumor; Esters; Humans; Isomers; Leucine; Lipid Peroxidation - drug effects; Male; Medical sciences; Melatonin; Methionine; Perezone; Pharmacology. Drug treatments; Rats; Rats, Wistar; Sesquiterpenes - chemical synthesis; Sesquiterpenes - chemistry; Sesquiterpenes - pharmacology; Spectroscopy; Structure-Activity Relationship; thiobarbituric acid-reactive substances; tryptamine; Tryptophan; Tumor cell lines; valine; Perezone; Amino derivatives; Antioxidants; Amino acids; Cytotoxic; Evaluation; Aminoacid; Cytotoxicity; Antioxidant; Chemical synthesis
• ISSN: 0968-0896; 1464-3391
• DOI: 10.1016/j.bmc.2012.07.027

A series of eight amino derivatives (3a–h) from perezone 1 were prepared by nucleophilic addition of bioactive amines v.gr. melatonin, acetyl tryptamine, tryptophan and other amino acids esters (valine, leucine and methionine). Their structures were elucidated by spectroscopy data. The cytotoxic evaluation against four human tumor cell lines PC-3, K-562, HCT-15 and SKLU-1 was performed as well as the TBARS assay for antioxidant activity. The results suggest that 1 and its isomer 4 were highly active against all cell lines, 4 was twice as potent than 1 against PC-3 and HCT-15. The derivative 3a (IC50=7.5±0.3μM) was more active than 1 against HCT-15 whereas 3h was selective against K-562 with IC50=4.5±0.4μM. The TBARS assay has shown that 3c with IC50=5.564±0.24μM is a potent antioxidant with superior effect comparing to tocopherol and moreover was more active than the precursor molecule 1.
A series of eight amino derivatives (3a–h) from perezone 1 were prepared by nucleophilic addition of bioactive amines v.gr. melatonin, acetyl tryptamine, tryptophan and other amino acids esters (valine, leucine and methionine). Their structures were elucidated by spectroscopy data. The cytotoxic evaluation against four human tumor cell lines PC-3, K-562, HCT-15 and SKLU-1 was performed as well as the TBARS assay for antioxidant activity. The results suggest that 1 and its isomer 4 were highly active against all cell lines, 4 was twice as potent than 1 against PC-3 and HCT-15. The derivative 3a (IC50=7.5±0.3μM) was more active than 1 against HCT-15 whereas 3h was selective against K-562 with IC50=4.5±0.4μM. The TBARS assay has shown that 3c with IC50=5.564±0.24μM is a potent antioxidant with superior effect comparing to α-tocopherol and moreover was more active than the precursor molecule 1.