116143-02-3Relevant articles and documents
Exploring Derivatives of Quinazoline Alkaloid l-Vasicine as Cap Groups in the Design and Biological Mechanistic Evaluation of Novel Antitumor Histone Deacetylase Inhibitors
Ahmad, Mudassier,Aga, Mushtaq A.,Bhat, Javeed Ahmad,Kumar, Brijesh,Rouf, Abdul,Capalash, Neena,Mintoo, Mubashir Javeed,Kumar, Ashok,Mahajan, Priya,Mondhe, Dilip Manikrao,Nargotra, Amit,Sharma, Parduman Raj,Zargar, Mohmmad Afzal,Vishwakarma, Ram A.,Shah, Bhahwal Ali,Taneja, Subhash Chandra,Hamid, Abid
, p. 3484 - 3497 (2017/05/05)
l-Vasicine is a quinazoline alkaloid with an electron dense ring and additional functionalities in its structure. Employing target oriented synthesis (TOS) based on in silico studies, molecules with significant docking scores containing different derivatives of l-vasicine as caps were synthesized. Interestingly, one molecule, i.e., 4a, which contained 3-hyroxypyrrolidine as a cap group and a six carbon long aliphatic chain as a linker was found to inhibit HDACs. 4a showed more specificity toward class I HDAC isoforms. Also 4a was found to be less cytotoxic toward normal cell lines as compared to cancer cell lines. 4a inhibited cancer cell growth and induced cell death by various mechanisms. However, 4a was found to induce cell death independent of ROS generation, and unlike many natural product based HDAC inhibitors, 4a was found to be nontoxic under in vivo conditions. Importantly, we for the first time report the possibility of using a 3-hydroxypyrrolidine cap for the synthesis of HDAC inhibitors with good potency.
3-Hydroxypyrrolidine and (3,4)-dihydroxypyrrolidine derivatives: Inhibition of rat intestinal α-glucosidase
Carreiro, Elisabete P.,Louro, Patrícia,Adriano, Gizé,Guedes, Romina A.,Vannuchi, Nicholas,Costa, Ana R.,Antunes, Célia M.M.,Guedes, Rita C.,Burke
, p. 81 - 88 (2014/06/09)
Thirteen pyrrolidine-based iminosugar derivatives have been synthesized and evaluated for inhibition of α-glucosidase from rat intestine. The compounds studied were the non-hydroxy, mono-hydroxy and dihydroxypyrrolidines. All the compounds were N-benzylated apart from one. Four of the compounds had a carbonyl group in the 2,5-position of the pyrrolidine ring. The most promising iminosugar was the trans-3,4-dihydroxypyrrolidine 5 giving an IC50 of 2.97 ± 0.046 and a KI of 1.18 mM. Kinetic studies showed that the inhibition was of the mixed type, but predominantly competitive for all the compounds tested. Toxicological assay results showed that the compounds have low toxicity. Docking studies showed that all the compounds occupy the same region as the DNJ inhibitor on the enzyme binding site with the most active compounds establishing similar interactions with key residues. Our studies suggest that a rotation of ～90° of some compounds inside the binding pocket is responsible for the complete loss of inhibitory activity. Despite the fact that activity was found only in the mM range, these compounds have served as simple molecular tools for probing the structural features of the enzyme, so that inhibition can be improved in further studies.
PROCESS FOR THE PREPARATION OF OPTICALLY ACTIVE N-BENZYL-3 HYDROXYPYRROLIDINES
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, (2012/05/04)
The present invention relates to a facile, highly efficient and economical process for the preparation of optically active N-benzyl-3-hydroxypyrrolidine in high yield from a naturally occurring alkaloid vasicine. The natural alkaloid vasicine is used as a precursor of (S)—N-benzyl-3-hydroxypyrrolidine and (R)—N-benzyl-3-hydroxypyrrolidines which can easily be sourced from the medicinal plant Adatoda vasica by the method known in the art and transformed to optical isomers (R) and (S)—N-benzyl-3-hydroxypyrrolidine by the method described in the present invention.
