title: Solvent-free synthesis of bacillamide analogues as novel cytotoxic and anti-inflammatory agents.
abstract: Synthesis of fourteen analogues of bacillamide, a bioactive tryptamide alkaloid of marine origin, has been accomplished through a highly efficient convergent route. The present solvent-free protocol involves the formation of thiazole ring in the initial step followed by amide coupling between substituted ethyl 2-alkyl/aryl/heteroaryl/amino/aminoarylthiazole-4-carboxylates and tryptamine in presence of 2-hydroxy-4,6-dimethylpyrimidine, a solid phase catalyst to yield N-[2-(1H-indol-3-yl)ethyl]-2-alkyl/aryl/heteroaryl/amino/aminoarylthiazole-4-carboxamides as bacillamide analogues having structural variation at position-2 of thiazole ring. Bacillamide and its analogues were evaluated for their cytotoxic activity against three cancer cell lines (HCT-116, MDA-MD-231 and JURKAT cell lines) using colorimetric cell proliferation assay. Compounds 17a and 17b exhibited potent anti-cell proliferation activity with IC50 values in the range of ∼3.0 μM and ∼0.1-0.6 μM, respectively against these cell lines. Preliminary mechanism of action studies indicates that these compounds initiate caspase dependent apoptosis. Also, compounds 16d, 16f, 17a and 17d exhibited excellent anti-inflammatory activity comparable to well-known NSAID indomethacin and better to bacillamide, when evaluated using carrageenan induced rat hind paw oedema method.
authors: Department of Chemistry, Kurukshetra University, Kurukshetra, 136119, India.
authors: Sunil
authors: S
authors: Kumar
authors: Department of Chemistry, Kurukshetra University, Kurukshetra, 136119, India. Electronic address: ranjanaaggarwal67@gmail.com.
authors: Ranjana
authors: R
authors: Aggarwal
authors: Department of Chemistry, Kurukshetra University, Kurukshetra, 136119, India.
authors: Virender
authors: V
authors: Kumar
authors: Department of Natural Sciences, UH-Downtown, Houston, TX, 77002, USA.
authors: Rachna
authors: R
authors: Sadana
authors: Department of Natural Sciences, UH-Downtown, Houston, TX, 77002, USA.
authors: Bhumi
authors: B
authors: Patel
authors: Department of Pharmaceutical Sciences, Kurukshetra University, Kurukshetra, 136119, India.
authors: Pawan
authors: P
authors: Kaushik
authors: Department of Pharmaceutical Sciences, Kurukshetra University, Kurukshetra, 136119, India.
authors: Dhirender
authors: D
authors: Kaushik
mesh_terms: D000818:Animals; D000894:Anti-Inflammatory Agents, Non-Steroidal / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology*; D000970:Antineoplastic Agents / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology*; D017209:Apoptosis / Q000187:drug effects; D045744:Cell Line, Tumor; D049109:Cell Proliferation / Q000187:drug effects; D060326:Chemistry Techniques, Synthetic; D055772:Green Chemistry Technology; D006801:Humans; D051381:Rats; D013329:Structure-Activity Relationship; D013844:Thiazoles / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology*
chemical_list: D000894:Anti-Inflammatory Agents, Non-Steroidal; D000970:Antineoplastic Agents; D013844:Thiazoles
keywords: 2-Hydroxy-4,6-dimethylpyrimidine; Anti-inflammatory activity; Bacillamide; Cytotoxic activity; Solvent-free synthesis; Tryptamide thiazole