178114-23-3Relevant academic research and scientific papers
E-pharmacophore guided discovery of pyrazolo[1,5-c]quinazolines as dual inhibitors of topoisomerase-I and histone deacetylase
Amrutkar, Suyog,Ansari, Arshad J.,Banerjee, Uttam C.,Joshi, Gaurav,Kalra, Sourav,Kumar, Raj,Kumar, Santosh,Sawant, Devesh M.,Sharma, Praveen,Sharma, Sadhana,Sharon, Ashoke,Singh, Pankaj Kumar,Singh, Sandeep,Yadav, Umesh Prasad
, (2019)
In the quest to ameliorate the camptothecin (CPT) downsides, we expedite to search for stable non-CPT analogues among 11 motifs of pyrazoloquinazolines reported. E-pharmacophore drug design approach helped filtering out pyrazolo[1,5-c]quinazolines as Topoisomerase I (TopoI) ‘interfacial’ inhibitors. Three compounds, 3c, 3e, and 3l were shown to be potent non-intercalating inhibitors of TopoI specifically and showed cancer cell-specific cytotoxicity in lung, breast and colon cancer cell lines. The compounds induced cell cycle arrest at S-phase, mitochondrial cell death pathway and modulated oxidative stress in cancer cells. Furthermore, a preliminary study was conducted to explore the feasibility of these compounds to be developed as dual TopoI-HDAC1 (histone deacetylase 1) inhibitors (4a) to combat resistance. Compound 4a was found to possess dual inhibitory capabilities in-vitro. Cytotoxic potential of 4a was found to be significantly higher than parent compound in 2D as well as 3D cancer cell models. Probable binding modes of 4a with TopoI and HDAC1 active sites were examined by molecular modelling.
Anticancer activity of dihydropyrazolo[1,5-c]quinazolines against rat C6 glioma cells via inhibition of topoisomerase II
Kaur, Gagandeep,Cholia, Ravi P.,Joshi, Gaurav,Amrutkar, Suyog M.,Kalra, Sourav,Mantha, Anil K.,Banerjee, Uttam C.,Kumar, Raj
, (2018/05/14)
The design and synthesis of dihydropyrazolo[1,5-c]quinazolines (1a–h) as human topoisomerase II (TopoII) catalytic inhibitors are reported. The compounds were investigated for their antiproliferative activity against the C6 rat glial cell line. Two compou
Synthesis and xanthine oxidase inhibitory activity of 5,6-dihydropyrazolo/pyrazolo[1,5-c]quinazoline derivatives
Kumar, Deependra,Kaur, Gagandeep,Negi, Arvind,Kumar, Sanjeev,Singh, Sandeep,Kumar, Raj
, p. 57 - 64 (2015/01/08)
Some 5,6-dihydropyrazolo/pyrazolo[1,5-c]quinazoline derivatives were rationally designed, synthesized and evaluated for in vitro xanthine oxidase inhibitory activity for the first time. Some notions about structure activity relationships are presented. Th
Benzodiazepine binding activity of some tricyclic heteroatomic systems to define the hydrogen bonding strength of the proton donors of the receptor site
Colotta,Catarzi,Varano,Melani,Filacchioni,Cecchi,Galli,Costagli
, p. 223 - 229 (2007/10/03)
Comparison of the benzodiazepine receptor affinities of some known and newly synthesized tricyclic derivatives of similar size and shape, and bearing the same pharmacophoric descriptors allowed us to suggest the different hydrogen bonding power of the proton donors of the benzodiazepine receptor recognition site. In particular, we propose, according to a previous model, that the lack of the a1 acceptor, which corresponds to a weak hydrogen donor of the receptor site, is not crucial for receptor-ligand interaction but, like the hydrogen donor d, only affects the potency. On the contrary, the presence of a proton acceptor atom in the a2 area is essential for the anchoring of our tricyclic derivatives to the benzodiazepine receptor recognition site.
