Novel Quinazolin‐4(3H)‐one/Schiff Base Hybrids as Antiproliferative and Phosphodiesterase 4 Inhibitors: Design, Synthesis, and Docking Studies

Abstract

A novel series of quinazolin-4(3H)-one/Schiff base hybrids was rationally designed and synthesized. The prepared compounds were evaluated for in vitro activity to inhibit phosphodiesterase 4 (PDE4), where several of them showed good-to-moderate activity compared to rolipram. Compound 7 showed potent PDE4 inhibition in this series, with an IC50 of 1.60 µM. Compounds that showed PDE4 inhibition were further assessed for antiproliferative activity using different human tumor cell lines. Compound 10 exhibited significant antiproliferative activity with IC50 values of 140, 79, and 320 nM in breast, lung, and colon tumor cells, respectively. Docking of compound 7 in the active site of PDE4B illustrates its possible binding mode and provides insight for further optimizations of this novel scaffold for inhibiting PDE4.

Quinazoline-Schiff base conjugates: in silico study and ADMET predictions as multi-target inhibitors of coronavirus (SARS-CoV-2) proteins

“…We previously reported the design and synthesis of a class of 3H-quinazolin-4-one/Schiff base conjugates and evaluated them in terms of their PDE 4B activity. 35 Based on the above ndings, as the most active derivatives of this series were trihydroxyphenyl Schiff bases, we thought that these compounds would be ideal drugs for the treatment of COVID-19 ( Fig. 4).…”

Design and Synthesis of Substituted Pyridazinone‐1‐Acetylhydrazones as Novel Phosphodiesterase 4 Inhibitors

“…These observations show that these compounds are bound to the PDE4B active site in a similar manner to other selective inhibitors . Additionally, this docking experiment shows that compounds as 6 or 12 are existing as two 4‐methoxyphenylpyridazinone units that individually contribute to the enzyme binding.…”

Quinazolin-4(3H)-ones and 5,6-Dihydropyrimidin-4(3H)-ones from β-Aminoamides and Orthoesters

“…This compound was prepared from 2-aminobenzhydrazide (100 mg, 0.67 mmol), triethyl orthobenzoate (300 mg, 303 µL, 1.34 mmol) and acetic acid (121 mg, 115 µL, 2.01 mmol) in absolute ethanol (2 mL) at 110 °C for 24 h. Yield: 151 mg (95%) as a tan solid, m.p. 160–161 °C (lit [ 53 ] m.p. 181–182 °C); IR (CHCl 3 ): 3435, 3316, 1612 cm −1 ; 1 H-NMR (400 MHz, CDCl 3 ): δ 8.15 (m, 2H), 7.87 (dd, J = 8.0, 1.5 Hz, 1H), 7.55 (m, 3H), 7.31 (ddd, J = 8.4, 7.2, 1.5 Hz, 1H), 6.82 (d, J = 8.4 Hz, 1H), 6.80 (td, J = 7.9, 1.1 Hz, 1H), 5.90 (br s, 2H); 13 C-NMR (101 MHz, CDCl 3 ): δ 164.6, 162.8, 147.1, 132.5, 131.7, 129.1, 127.8, 126.9, 123.9, 116.8, 116.2, 105.8; HRMS (ESI): m/z for C 14 H 11 N 3 O [M + 1] + : calcd.…”