66645-09-8Relevant academic research and scientific papers
Synthesis of Pyrimido[1,2-a]benzimidazol-4(10H)-one Derivatives and Evaluation of their Interactions with DNA
Da Settimo,Primofiore,Da Settimo,Marini,Taliani,Salerno,Dalla Via
, p. 1091 - 1096 (2003)
The synthesis of new derivatives of the planar tricyclic pyrimido[1,2-a]benzimidazole system featuring protonable side chains in the 3 and/or 10 positions is described. The reported literature procedures for the preparation of the intermediate 3-ethoxycarbonylpyrimido[1,2-a]benzimidazol-4(10H)2-a]benzimidazol-4(10H)-one 15, starting from 2-aminobenzimidazole 18 and diethyl ethoxymethylenemalonate, were revised. The interaction with DNA, the intrinsic binding constants, and the antiproliferative activity of a number of compounds (1-8, 10, 11) were preliminarly investigated.
Novel 4-oxo-4,10-dihydrobenzo[4,5]imidazo[1,2-a]pyrimidine-3-carboxylic acid derivatives as hiv-1 integrase inhibitors: Synthesis, docking studies, molecular dynamics simulation and biological activities
Hajimahdi, Zahra,Vahabpour, Rouhollah,Zadeh, Elnaz Ebrahim,Zarghi, Afshin,beirami, Amirreza Dowlati
, p. 1060 - 1071 (2021/11/30)
Background: HIV-1 integrase (IN) has been considered as an important target for the development of novel anti-HIV-1 drugs. Objective: The aim of this study was to design novel groups of HIV IN inhibitors. Methods: In this study, we presented a novel series of 4-oxo-4,10-dihydrobenzo[4,5]imidazo[1,2-a]pyrimidine-3-carboxylic acid derivatives by structural modification of N-arylindole β-diketoacids as a well-known group of IN inhibitors. Results: Based on in-vitro anti-HIV-1 activity in a cell-based assay, compounds 5, 6a and 6k displayed moderate to good inhibitory activity with EC50 values of 4.14, 1.68 and 0.8 μM, respectively. However, integrase inhibition assay showed that most of the analogues did not have significant effects against integrase enzyme except compound 5 with an IC50 value of 45 μM. Our results indicated that compound 6k was the best one among synthesized compounds with an EC50 of 0.8 μM and SI of 175. Docking and molecular dynamics simulation studies were also performed to provide some insights into the probable mechanism of tested compounds. Conclusion: These findings suggest that 4-oxo-4,10-dihydrobenzo[4,5]imidazo[1,2-a]pyrimidine-3-carboxylic acid derivatives may consider as promising lead compounds for the development of new anti-HIV-1 drugs.
