5451-40-1Relevant articles and documents
Purine-benzimidazole hybrids: Synthesis, single crystal determination and in vitro evaluation of antitumor activities
Sharma, Alka,Luxami, Vijay,Paul, Kamaldeep
, p. 414 - 422 (2015)
In an effort to identify novel compounds for the treatment of cancer, a diverse array of potential bioactive hybrid, purine-benzimidazole was synthesized in good yields through nucleophilic substitution at C6 position of purine ring with versatile cyclic amines at C2 position. The structures of newly prepared compounds were confirmed by IR, 1H, 13C NMR, mass spectroscopy and, in case of 19, by single crystal Xray diffraction analysis. The newly synthesized compounds were evaluated against 60 human tumour cell lines at one dose concentration level. Compound 6 exhibited significant growth inhibition and was evaluated as 60 cell panel at five dose concentration levels. Compound 6 proved to be 1.25 fold more active than the positive control 5-FU, with GI50 value of 18.12 μM (MG-MID). Interaction of the compounds with Aurora-A enzyme involved in the process of propagation of cancer, has also been investigated. Compound 6 showed selectivity towards Aurora-A kinase inhibition with IC50 value of 0.0l mM. Molecular docking studies in the active binding site provided theoretical support for the experimental biological data acquired.
Development of a Novel and Scalable Process for the Synthesis of a Key Cangrelor Intermediate
Guvvala, Vinodh,Subramanian, Venkatesan Chidambaram,Anireddy, Jayashree
, p. 530 - 536 (2019/11/19)
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Design, Synthesis, and Immunological Evaluation of a Multicomponent Construct Based on a Glycotripeptoid Core Comprising B and T Cell Epitopes and a Toll-like Receptor 7 Agonist That Elicits Potent Immune Responses
Szekely, Thomas,Roy, Olivier,Dériaud, Edith,Job, Aurélie,Lo-Man, Richard,Leclerc, Claude,Taillefumier, Claude
supporting information, p. 9568 - 9582 (2018/11/23)
We present here for the first time the synthesis and immunological evaluation of a fully synthetic three-component anticancer vaccine candidate that consists of a β-glycotripeptoid core mimicking a cluster of Tn at the surface of tumor cells (B epitope), conjugated to the OVA 323-339 peptide (T-cell epitope) and a Toll-like receptor 7 (TLR7) agonist for potent adjuvanticity. The immunological evaluation of this construct and of precursor components demonstrated the synergistic activity of the components within the conjugate to stimulate innate and adaptive immune cells (DCs, T-helper, and B-cells). Surprisingly, immunization of mice with the tricomponent GalNAc-based construct elicited a low level of anti-Tn IgG but elicited a very high level of antibodies that recognize the TLR7 agonist. This finding could represent a potential vaccine therapeutic approach for the treatment of some autoimmune diseases such as lupus.
Design, synthesis and evaluation of 4-aminoquinoline-purine hybrids as potential antiplasmodial agents
Reddy, P. Linga,Khan, Shabana I.,Ponnan, Prija,Tripathi, Mohit,Rawat, Diwan S.
, p. 675 - 686 (2016/12/14)
A novel series of 4-aminoquinoline-purine hybrids were synthesized and assessed for their antiplasmodial activity against CQ-sensitive and CQ-resistant strains of P. falciparum. It was envisaged that linking of the 4-aminoquinoline pharmacophore (targeting heme-detoxification pathway of malarial parasite) with the purine functionality (targeting plasmodial HG(X)PRT enzyme) will produce a hybrid antiplasmodial agent with increased potency. The synthesized hybrids displayed good antiplasmodial activities against both the sensitive and resistant strains of P. falciparum with up to six-fold better activity (compound 10i, IC50: 0.08?μM) compared to the reference drug CQ (IC50: 0.5?μM) against the resistant strain. The synthesized compounds were also checked for their cytotoxicity towards mammalian cells and with the exception of two compounds out of the twenty synthesized hybrids, all others were non-cytotoxic up to 11.86?μM concentration. Mechanistic heme-binding studies were performed to identify the mechanism of action of the synthesized molecules and good binding interactions were observed. Computational docking studies showed that the most active hybrids dock well within the binding site of HGPRT protein. In silico ADME predictions of the most active hybrids showed that these compounds possess good pharmacokinetic behavior.
