1899-48-5Relevant articles and documents
Structure-Activity Relationship Studies of Isomeric 2,4-Diaminoquinazolines on β-Amyloid Aggregation Kinetics
Mohamed, Tarek,Shakeri, Arash,Tin, Gary,Rao, Praveen P. N.
, p. 502 - 507 (2016)
A library of isomeric 2,4-diaminoquinazoline (DAQ) derivatives were synthesized and evaluated for antiaggregation potential toward Aβ40/42. Structure-activity relationship data identified compound 3k (N4-(4-bromobenzyl)quinazoline-2,4-diamine) with a 4-bromobenzyl substituent as the most potent inhibitor (Aβ40 IC50 = 80 nM) and was almost 18-fold more potent compared to the reference agent curcumin (Aβ40 IC50 = 1.5 μM). The corresponding N2-isomer 4k (N2-(4-bromobenzyl)quinazoline-2,4-diamine) was also able to prevent Aβ aggregation (Aβ40 IC50 = 1.7 μM). However, compound 4k exhibited superior inhibition of Aβ42 aggregation (Aβ42 IC50 = 1.7 μM) compared to compound 3k (Aβ42 IC50 = 14.8 μM) and was ～1.8-fold more potent compared to curcumin (Aβ42 IC50 = 3.1 μM). These results were supported by Aβ aggregation kinetics investigations and transmission electron microscopy studies, which demonstrate the suitability of DAQ ring system to develop antiamyloid agents as pharmacological tools to study Aβ aggregation.
Dual and selective inhibitors of pteridine reductase 1 (PTR1) and dihydrofolate reductase-thymidylate synthase (DHFR-TS) from Leishmania chagasi
Teixeira, Bárbara Velame Ferreira,Teles, André Lacerda Braga,Silva, Suellen Gon?alves da,Brito, Camila Carane Bitencourt,Freitas, Humberto Fonseca de,Pires, Acássia Benjamim Leal,Froes, Thamires Quadros,Castilho, Marcelo Santos
, p. 1439 - 1450 (2019)
Leishmaniasis is a tropical disease found in more than 90 countries. The drugs available to treat this disease have nonspecific action and high toxicity. In order to develop novel therapeutic alternatives to fight this ailment, pteridine reductase 1 (PTR1) and dihydrofolate reductase-thymidylate synthase (DHF-TS) have been targeted, once Leishmania is auxotrophic for folates. Although PTR1 and DHFR-TS from other protozoan parasites have been studied, their homologs in Leishmania chagasi have been poorly characterized. Hence, this work describes the optimal conditions to express the recombinant LcPTR1 and LcDHFR-TS enzymes, as well as balanced assay conditions for screening. Last but not the least, we show that 2,4 diaminopyrimidine derivatives are low-micromolar competitive inhibitors of both enzymes (LcPTR1 Ki = 1.50–2.30 μM and LcDHFR Ki = 0.28–3.00 μM) with poor selectivity index. On the other hand, compound 5 (2,4-diaminoquinazoline derivative) is a selective LcPTR1 inhibitor (Ki = 0.47 μM, selectivity index = 20).
Fragment based search for small molecule inhibitors of HIV-1 Tat-TAR
Zeiger, Mirco,Stark, Sebastian,Kalden, Elisabeth,Ackermann, Bettina,Ferner, Jan,Scheffer, Ute,Shoja-Bazargani, Fatemeh,Erdel, Veysel,Schwalbe, Harald,G?bel, Michael W.
supporting information, p. 5576 - 5580 (2015/01/08)
Basic molecular building blocks such as benzene rings, amidines, guanidines, and amino groups have been combined in a systematic way to generate ligand candidates for HIV-1 TAR RNA. Ranking of the resulting compounds was achieved in a fluorimetric Tat-TAR
