4364-74-3Relevant academic research and scientific papers
Synthesis, Antileishmanial Activity and In Silico Studies of Aminoguanidine Hydrazones (AGH) and Thiosemicarbazones (TSC) Against Leishmania chagasi Amastigotes
Alexandre-Moreira, Magna S.,Aquino, Pedro G. V.,Bourguignon, Jean-Jacques,Bri-Card, Jacques,Freitas, Johnnatan D.,Meneghetti, Mario R.,Nascimento, Igor J. S.,Queiroz, Aline C.,Rodrigues, Klinger A. F.,Rodrigues, Raiza R. L.,Santos, Mariana S.,Schmitt, Martine,de Aquino, Thiago M.,Araújo, Morgana V.,Fran?a, Paulo H. B.,Rodrigues, érica E. E. S.,Santos-Júnior, Paulo F. S.,da Silva-Júnior, Edeildo F.,de Araújo-Júnior, Jo?o X.
, p. 151 - 169 (2022/02/05)
Background: Leishmaniasis is a worldwide health problem, highly endemic in developing countries. Among the four main clinical forms of the disease, visceral leishmaniasis is the most se-vere, fatal in 95% of cases. The undesired side-effects from first-li
Enriching biologically relevant chemical space around 2-aminothiazole template for anticancer drug development
Titus, Sarah,Sreejalekshmi, Kumaran G.
, p. 23 - 36 (2018/04/19)
Combinatorial library based on a biologically relevant core template, 2-aminothiazole, with immense scope of diversity multiplication was designed for anticancer therapeutics. The diversity elements were incorporated through azomethine linkage on C4 hydrazine terminus in 5-benzoyl-2-arylamino-1,3-thiazole using isopropyl, isobutyl, cyclohexyl, and benzyl fragments and enrichment of chemical space therein was evaluated. Molecular docking of an in-house 200-member virtual library in anticancer target proteins- estrogen receptor (3ERT), cyclin dependent kinase (3FDN), and Aurora kinase (3LAU), identified selective binding of the compounds as ATP competitive inhibitors of 3LAU. The synthetic access to the compounds was realized through a facile and economically viable [4 + 1] ring synthesis strategy employing commercially available reagents. The in vitro cytotoxicity of selected members against human cancer cell lines indicated the potential of the designed scaffold in anticancer drug discovery, where compounds 2b, 3b, and 4b were found to be active against MCF-7 and A549 cell lines in less than ten micro molar concentrations. Moreover the predicted physicochemical properties pointed to the drug appropriateness for most of these molecules, that they obey the rule of five (RO5). Thus we present 2-alkyl/arylamino-4-alkylidene/arylidenehydrazino-5-benzoyl-1,3-thiazoles as a prospective and expandable skeleton for diversity oriented synthesis and in the discovery of selective Aurora kinase inhibitors.
One-pot four-component synthesis of 4-hydrazinothiazoles: Novel scaffolds for drug discovery
Titus, Sarah,Sreejalekshmi, Kumaran G.
supporting information, p. 5465 - 5467 (2014/12/11)
One pot ring synthesis of novel 4-hydrazinothiazoles through sequential four-component route employing carbonyl compounds, aminoguanidine, isothiocyanates, and α-haloketones was accomplished under mild reaction conditions. Base-assisted eliminative aromatization in the [4+1] ring synthesis shed light on interesting leaving group propensities of amine versus hydrazine resulting in the exclusive formation of the title compounds with immense potential as scaffolds for drug discovery. Hydrazone deprotection was effected by acylation which subsequently provided a new set of diacylated molecular systems with a wider scope as chemical handles in the design of thiazolyl drug candidates.
A facile, sequential multicomponent approach to N-aminoamidinothioureas- versatile synthons to bioactive heterocycles
Sreejalekshmi
experimental part, p. 1830 - 1837 (2010/11/16)
A sequential, three-component approach for the rapid and convenient one-pot synthesis of N-aminoamidinothioureas is reported. The improved synthetic strategy involves the selective blocking of amino functionality in aminoguanidine by Schiff base formation with carbonyl compounds to generate corresponding N-(alkylidene/arylidene)aminoguanidines and their subsequent in situ condensation with isothiocyanate. The structural motif incorporates three points for diversity multiplication, making it a suitable candidate for combinatorial synthesis. The generality of the improved procedure was established by synthesizing a series of diverse compounds through solution phase parallel synthesis by varying the carbonyl and isothiocyanate components. The newly synthesized compounds were characterized by spectral methods. The developed synthetic procedure employs mild reaction conditions, and individual steps are carefully optimized for easy automation. Copyright
