931098-08-7Relevant articles and documents
Design, computational studies, synthesis and biological evaluation of thiazole-based molecules as anticancer agents
Anuradha,Patel, Sagarkumar,Patle, Rajkumar,Parameswaran, Preethi,Jain, Alok,Shard, Amit
, p. 20 - 30 (2019/04/25)
Background: Abolition of cancer warrants effective treatment modalities directed towards specific pathways dysregulated in tumor proliferation and survival. The antiapoptotic Bcl-2 proteins are significantly altered in several tumor types which position them as striking targets for therapeutic intervention. Here we designed, computationally evaluated, synthesized, and biologically tested structurally optimized thiazole-based small molecules as anticancer agents. Methods: The virtually designed 200 molecules were subjected to rigorous docking and in silico ADME-Toxicity studies. Out of this, 23 skeletally diverse thiazole-based molecules which passed pan assay interference compounds (PAINS) filter and were synthetically feasible were synthesized in 3 steps using cheap and readily available reagents. The molecules were in vitro evaluated against Bcl-2-Jurkat, A-431 cancerous cell lines and ARPE-19 cell lines. Molecular Dynamics (MD) simulation studies were performed to analyse conformational changes induced by ligand 32 in Bcl-2. Flow cytometry analysis of compound 32 treated Bcl-2 cells was done to check apoptosis. Results: The molecules exhibited appreciable interactions with Bcl-2 and were having acceptable drug like properties as tested in silico. The multi step synthesis yielded 23 skeletally diverse thiazole-based molecules in up to 80% yield. The molecules simultaneously inhibited Bcl-2 Jurkat cells in vitro without causing detectable toxicity to normal cells (ARPE-19 cells). Among them molecules 32, 50, 53, 57 and 59 showed considerable activities against Bcl-2 Jurkat and A-431cell lines at concentrations ranging from 32–46 μM and 34–52 μM, respectively. The standard doxorubicin exhibited IC50 in Bcl-2 Jurkat and A-431cell lines at 45.87 μM and 42.37 μM, respectively. The molecule 32, almost equipotent in both the cell lines was subjected to molecular dynamics (MD) simulation with Bcl-2 protein (4IEH). It was shown that 32 interacted with protein majorly via hydrophobic interactions and few H-bonding interactions. Fluorescence-activated cell sorting (FACS) analysis established that molecule is dragging cancerous cells towards apoptosis. Discussion and conclusion: The chemical intuition was checked by computation coupled with biological results confirmed that thiazole-based hits have the potential to be developed downstream into potent and safer leads against antiapoptotic Bcl-2 cells.
Discovery of 2-aminoimidazole and 2-amino imidazolyl-thiazoles as non-xanthine human adenosine A3 receptor antagonists: SAR and molecular modeling studies
Pandya, Amit N.,Baraiya, Arshi B.,Jalani, Hitesh B.,Pandya, Dhaivat,Kaila, Jitendra C.,Kachler, Sonja,Salmaso, Veronica,Moro, Stefano,Klotz, Karl-Norbert,Vasu, Kamala K.
, p. 676 - 684 (2018/05/03)
A small-molecule combinatorial library of 24 compounds with 2-aminoimidazole and 2-aminoimidazolyl-thiazole derivatives was synthesized using a 2-chloro trityl resin. The generated compound library was tested against all the human adenosine receptors subt
Mercury(II) chloride-mediated desulphurization of amidinothioureas: Synthesis and antimicrobial activity of 3-amino-1,2,4-triazole derivatives
Yerande, Swapnil G.,Baviskar, Chetna D.,Newase, Kiran M.,Wang, Wei,Wang, Kan,D?mling, Alexander
, p. 1883 - 1887 (2015/01/09)
The synthesis of 3-amino-1,2,4-triazole via mercury(II) chloride-mediated cyclization of amidinothiourea is described. This procedure offers a general and efficient route to synthesize the title compound by 3 + 2 annulation reaction. On the basis of the l
A diversified assembly of 1,2,4-oxadiazol-3-amines: Metallic thiophile catalyzed chemoselective one-pot reaction of aryl isothiocyanates, amidines/guanidines, and hydroxylamine
Jalani, Hitesh B.,Sudarsanam, V.,Vasu, Kamala K.
, p. 3378 - 3386,9 (2012/12/12)
An efficient one-pot synthesis of 1,2,4-oxadiazol-3-amines from simple starting materials, isothiocyanates, amidines/guanidines, and hydroxylamine, is described. The reaction is facilitated by metallic-thiophile-assisted desulfurization of in situ formed amidino- or guanidinothiourea to give chemoselectively N-hydroxyguanidine intermediates that give exclusively various 1,2,4-oxadiazol-3-amines in good to excellent yields. The reaction mechanistic pathway may proceed through an intramolecular 5-exo-trig cyclization.
A convenient one-pot synthesis of trisubstituted 1,3,5-triazines through intermediary amidinothioureas
Kaila, Jitendra C.,Baraiya, Arshi B.,Pandya, Amit N.,Jalani, Hitesh B.,Sudarsanam,Vasu, Kamala K.
supporting information; experimental part, p. 1486 - 1489 (2010/04/27)
A thiophile-promoted one-pot synthesis of trisubstituted 1,3,5-triazines starting from isothiocyanates, N,N-diethylamidines, and carbamidines has been studied. The reaction proceeds through the formation of intermediary amidinothioureas, which react with
Design, synthesis and characterization of novel 2-(2,4-disubstituted-thiazole-5-yl)-3-aryl-3H-quinazoline-4-one derivatives as inhibitors of NF-κB and AP-1 mediated transcription activation and as potential anti-inflammatory agents
Giri, Rajan S.,Thaker, Hardik M.,Giordano, Tony,Williams, Jill,Rogers, Donna,Sudersanam, Vasudevan,Vasu, Kamala K.
body text, p. 2184 - 2189 (2009/09/30)
A series of 2-(2,4-disubstituted-thiazole-5-yl)-3-aryl-3H-quinazoline-4-one derivatives were designed and synthesized. Synthesized molecules were further evaluated for their inhibitory activity towards transcription factors NF-κB and AP-1 mediated transcr
