259735-07-4Relevant articles and documents
High-Throughput Screening of Reductive Amination Reactions Using Desorption Electrospray Ionization Mass Spectrometry
Cooks, R. Graham,Ferreira, Christina R.,Li, Yangjie,Logsdon, David L.,Paschoal Sobreira, Tiago Jose,Thompson, David H.
supporting information, p. 1647 - 1657 (2020/10/26)
This study describes the latest generation of a high-throughput screening system that is capable of screening thousands of organic reactions in a single day. This system combines a liquid handling robot with desorption electrospray ionization (DESI) mass spectrometry (MS) for a rapid reaction mixture preparation, accelerated synthesis, and automated MS analysis. A total of 3840 unique reductive amination reactions were screened to demonstrate the throughputs that are capable with the system. Products, byproducts, and intermediates were all monitored in full-scan mass spectra, generating a complete view of the reaction progress. Tandem mass spectrometry experiments were conducted to verify the identity of the products formed. The amine and electrophile reactivity trends represented in the data match what is expected from theory, indicating that the system accurately models the reaction performance. The DESI results correlated well with those generated using more traditional mass spectrometry techniques like liquid chromatography-mass spectrometry, validating the data generated by the system.
Gibbilimbol analogues as antiparasitic agents - Synthesis and biological activity against Trypanosoma cruzi and Leishmania (L.) infantum
Varela, Marina T.,Dias, Roberto Z.,Martins, Ligia F.,Ferreira, Daiane D.,Tempone, Andre G.,Ueno, Anderson K.,Lago, Jo?o Henrique G.,Fernandes, Jo?o Paulo S.
, p. 1180 - 1183 (2016/02/23)
The essential oils from leaves of Piper malacophyllum (Piperaceae) showed to be mainly composed by two alkenylphenol derivatives: gibbilimbols A and B. After isolation and structural characterization by NMR and MS data analysis, both compounds were evaluated against promastigote/amastigote forms of Leishmania (L.) infantum as well as trypomastigote/amastigote forms of Trypanosoma cruzi. The obtained results indicated that gibbilimbol B displayed potential against the tested parasites and low toxicity to mammalian cells, stimulating the preparation of several quite simple synthetic analogues in order to improve its activity and to explore the preliminary structure-activity relationships (SAR) data. Among the prepared derivatives, compound LINS03003 (n-octyl-4-hydroxybenzylamine) displayed the most potent IC50 values of 5.5 and 1.8 μM against amastigotes of T. cruzi and L. (L.) infantum, respectively, indicating higher activity than the natural prototype. In addition, this compound showed remarkable selectivity index (SI) towards the intracellular forms of Leishmania (SI = 13.1) and T. cruzi (SI = 4.3). Therefore, this work indicated that preparation of synthetic compounds structurally based in the bioactive natural products could be an interesting source of novel and selective compounds against these protozoan parasites.
