- Promising carboranylquinazolines for boron neutron capture therapy: Synthesis, characterization, and in vitro toxicity evaluation
-
Novel classes of structurally different boronated quinazolines were designed bearing 22-37% boron by weight for potential application in BNCT of tumors. Firstly, the o-carborane cage was linked to quinazoline at C-2 position via thioether linker: 2-S-(1,2
- Genady, Afaf R.
-
-
Read Online
- Novel click modifiable thioquinazolinones as anti-inflammatory agents: Design, synthesis, biological evaluation and docking study
-
Click chemistry was used to synthesize a new series of thioquinazolinone molecules equipped with propargyl moiety,1,2,3-triazolyl and isoxazolyl rings. Our design was based on merging pharmacophores previously reported to exhibit COX-2 inhibitory activities to a thioquinazolinone-privileged scaffold. The synthesized compounds were subjected to in vitro cyclooxygenase COX-1/COX-2 and 15-LOX inhibition assays. Compounds 2c, 3b, 3h, 3j, and 3k showed COX-2 inhibition with IC50 (μM) 0.18, 0.19, 0.11, 0.16 and 0.17 respectively. These values were compared to celecoxib (IC50 0.05 μM), diclofenac (IC50 0.8 μM) and indomethacin (IC50 0.49 μM) reference drugs. They also showed 15-LOX inhibition with IC50 (μM) 6.21, 4.33, 7.62, 5.21 and 3.98 respectively. These values were compared with Zileuton (IC50 2.41 μM) and Meclofenamate sodium (IC50 5.64 μM) as positive controls. These compounds were further challenged by PMA-induced THP-1 differentiation assay where compounds 2c and 3j inhibited monocyte to macrophage differentiation efficiently with IC50 values of 4.78 μM and 5.63 μM, respectively, compared to that of diclofenac sodium (4.86 μM). On the other hand, 3h demonstrated a significantly increased potency compared to diclofenac in this assay (IC50 = 0.13 μM). The same compounds exhibited significant in vivo anti-inflammatory effect as indicated by the formalin-induced rat-paw edema test. Docking experiments of compounds 2c, 3b, 3h, 3j, and 3k into COX-2 binding pocket have been conducted, where strong binding interactions have been identified and effective overall docking scores have been recorded. Their drug-likeness has been assessed using Molinspiration, Molsoft and Pre-ADMET software products.
- Moussa, Ghandoura,Alaaeddine, Rana,Alaeddine, Lynn M.,Nassra, Rasha,Belal, Ahmed S.F.,Ismail, Azza,El-Yazbi, Ahmed F.,Abdel-Ghany, Yasser S.,Hazzaa, Aly
-
p. 635 - 650
(2018/01/02)
-
- Synthesis, properties, and mass-spectrometric fragmentation of 2-thio derivatives of 3-arylquinazolin-4-ones
-
We have studied the reactions of alkylation, oxidation, and hydrolysis of 3-aryl-2-thioxoquinazolin-4-ones. Alkylation in an alkaline medium occurs exclusively at the sulfur atom. Oxidation by hydrogen peroxide leads to formation of 3-arylquinazoline-2,4-diones. The latter are also obtained in base or acid hydrolysis of the synthesized S-alkyl derivatives. When 3-aryl-2-thioxoquinazolin-4-ones are reacted with iodine, we obtain the disulfides, while the reaction with chlorine in hydrochloric acid leads to 2-chloroquinazolin-4-ones. Studying the mass spectrometric behavior of the compounds obtained made it possible to observe in the gas phase ring-chain isomerization of the heterocyclic ring, and also S-N migration of the propargyl radical in molecular ions of the S-propargyl derivatives.
- Azev,Golomolzin,Dyulcks,Klyuev,Yatluk
-
p. 356 - 361
(2008/09/21)
-