Synthesis and in vitro study of antiproliferative benzyloxy dihydropyrimidinones

Abstract

In this study, we report on antiproliferative benzyloxy dihydropyrimidinones (DHPMs) produced by the Biginelli reaction of benzyloxy benzaldehyde, urea, and diverse 1,3-diones. The reaction was catalyzed by lanthanum triflate and completed within 1-1.5 h, with 74-97% yield. The antiproliferative assay was carried out for all synthesized dihydropyrimidinones against six human solid tumor cell lines. Six compounds showed good antiproliferative activity with GI 50 values below 5 μM. Among all the synthesized compounds, the most potent derivative showed good antiproliferative activity against all cell lines with GI 50 values in the range of 1.1-3.1 μM. These DHPMs comply with druglikeness. Furthermore, ADMET prediction and the effect of P-glycoprotein on the antiproliferative activity were also studied. Overall, our method allows eco-friendly access to benzyloxy DHPMs as potential anticancer drugs.

Synthesis, crystal structure and in silico studies of novel 2,4-dimethoxy-tetrahydropyrimido[4,5-b]quinolin-6(7H)-ones

“…Catalyst-free synthesis of THPQs were also reported using absolute ethanol, 32 acetic acid, 33–35 and electrolysis in presence of alcohol. 36 In continuation of our work in multicomponent synthesis, 37–42 here, we reported the simple acetic acid-mediated multicomponent synthesis of novel PQs. This simple protocol generated 2,4-dimethoxy-THPQs 4(a–d) with good yield of products (68–73%).…”

Microwave-assisted multicomponent synthesis of antiproliferative 2,4-dimethoxy-tetrahydropyrimido[4,5-b]quinolin-6(7H)-ones

“…In this work, we developed novel pyrimidine and quinoline based heterocycles to develop a new potent antiproliferative agent. 2,3 Multicomponent reactions (MCRs) facilitated by microwave irradiation are an effective strategy from the perspective of green chemistry. 4 Microwave irradiation is a powerful tool in heterocyclic chemistry as well as drug discovery.…”

Catalyst-Free, Room-Temperature Accessible Regioselective Synthesis of Spiroquinolines and Their Antioxidant Study

“…In 2019, the same MCR was performed by Bhardwaj et al using TiO 2‑ based nanoparticles in water and achieved the same motif (Scheme ). These derivatives are formed because Meldrum’s acid commonly holds the exclusive ring-seized malonic acid part, which is generated by the loss of an acetone molecule, while the reaction with nucleophiles can be convoyed by the liberation of carbon dioxide. − …”