154128-82-2Relevant academic research and scientific papers
Cytotoxic activity of synthetic chiral amino acid derivatives
de Castro, Pedro P.,Siqueira, Raoni P.,Conforte, Luiza,Franco, Chris H.J.,Bressan, Gustavo C.,Amarante, Giovanni W.
, p. 193 - 200 (2019/12/28)
Cancer is a chronic degenerative disease considered one of the most important causes of death worldwide. In this context, a series of dual-protected amino acid derivatives was synthesized and evaluated as potential novel anticancer agents. The 40 derivatives were prepared in up to three reaction steps. The cytotoxic activities were screened in vitro against a panel of tumor and non-tumor cells using 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) assay. Among the synthesized derivatives, three of them showed promising activity against cancer cells with half-maximal inhibitory concentration (IC50) ranging between 1.7-6.1 μM. The most promising derivative, bearing both a lipophilic N-alkyl diamine moiety and a protected amino acid scaffold showed a selectivity index of 3.4 towards tumor cells. The N-alkyl diamine moiety seems to play a crucial role in the enhancement of the anticancer activity. On the other hand, the incorporation of an amino acid scaffold resulted in increase in the selectivity towards cancer cell lines.
Dual-protected amino acid derivatives as new antitubercular agents
de Castro, Pedro P.,Campos, Débora L.,Pavan, Fernando R.,Amarante, Giovanni W.
, p. 1576 - 1580 (2018/06/06)
Tuberculosis is an infectious disease with high incidence and growing drug-resistant rates. In an attempt to develop new antitubercular agents, 35 compounds were synthesized, most of them bearing a carbamate and enantiopure amino acid moiety. These compounds had their activity evaluated toward a Mycobacterium tuberculosis strain (ATCC 27294) and cytotoxicity against fibroblast MRC-5 cells (ATCC CCL-171). Three of the prepared derivatives presented a good antimicrobial inhibition and two of them a moderate cytotoxicity. The lipophilicity seems to play a vital role in the cell growth activity, with best results for the derivatives with a higher logP.
[...] - Orn (ClCH2NH) - AA - benzylamine, its synthesis, activity and application (by machine translation)
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Paragraph 0041; 0090; 0091, (2017/08/27)
The invention discloses the following formula of 13 for β - Carboline -3 - formyl - Orn (ClCH2 NH) - AA - NHCH2 C6 H5 (In the formula AA is selected from L - Arg, L - Asn, L - Asp, L - Glu, L - Gly, L - Ile, L - Leu, L - Met, L - Phe, L - Pro, L - Thr, L - Trp, L - Val residue), discloses a process for their preparation, discloses their inhibition of tumor cell growth, therefore this invention discloses their use as anti-tumor medicament. (by machine translation)
Benzylamide antagonists of protease activated receptor 2 with anti-inflammatory activity
Yau, Mei-Kwan,Liu, Ligong,Lim, Junxian,Lohman, Rink-Jan,Cotterell, Adam J.,Suen, Jacky Y.,Vesey, David A.,Reid, Robert C.,Fairlie, David P.
, p. 986 - 991 (2016/06/28)
Activation of protease activated receptor 2 (PAR2) has been implicated in inflammatory and metabolic disorders and its inhibition may yield novel therapeutics. Here, we report a series of PAR2 antagonists based on C-terminal capping of 5-isoxazolyl-l-cyclohexylalanine-l-isoleucine, with benzylamine analogues being effective new PAR2 antagonists. 5-Isoxazolyl-l-cyclohexylalanine-l-isoleucine-2-methoxybenzylamine (10) inhibited PAR2-, but not PAR1-, induced release of Ca2+(IC500.5 μM) in human colon cells, IL-6 and TNFα secretion (IC501-5 μM) from human kidney cells, and was anti-inflammatory in acute rat paw inflammation (ED505 mg/kg sc). These findings show that new benzylamide antagonists of PAR2 have anti-inflammatory activity.
Development of Potent Inhibitors of Botulinum Neurotoxin Type B
Anne, Christine,Turcaud, Serge,Quancard, Jean,Teffo, Franck,Meudal, Hervé,Fournié-Zaluski, Marie-Claude,Roques, Bernard P.
, p. 4648 - 4656 (2007/10/03)
Botulinum neurotoxins are the most potent toxins known to date. They are zinc-metalloproteases able to cleave selectively an essential component of neurotransmitter exocytosis, causing the syndrome of botulism characterized by a flaccid paralysis. There is a great interest in designing antagonists of the action of these toxins. One way is to inhibit their catalytic activity. In this study, we report the design of such inhibitors directed toward BoNT/B. A study of the S1 subsite specificity, using several β-amino thiols, has shown that this subsite prefers a p-carboxybenzyl moiety. The specificity of the S1′ and S2′ subsites was studied using two libraries of pseudotripeptides containing the S1 synthon derived from the best β-amino thiol tested. Finally, a selection of various non natural amino acids for the recognition of the "prime" domain led to the most potent inhibitor of BoNT/B described to date with a Ki value of 20 nM.
