Investigation of some benzoquinazoline and quinazoline derivatives as novel inhibitors of HCV-NS3/4A protease: biological, molecular docking and QSAR studies

Abstract

HCV NS3/A4 protease inhibitors are one of the best therapeutic targets for the identification of novel candidate drugs. A series of benzo[g]quinazolines and their quinazoline analogues were evaluated for their HCV-NS3/4A inhibitory activities.

Antiproliferative and Antiangiogenic Properties of New VEGFR-2-targeting 2-thioxobenzo[g]quinazoline Derivatives (In Vitro)

“…Using previously reported synthetic procedures for preparation of their analogues [ 13 , 17 , 23 ], the current 3-ethyl(methyl)-2-thioxobenzo[ g ]quinazolin-4(3 H )-ones ( 1 – 17 ) were obtained in good yields (see Section 3.1.1 ). The structures of all products were established using HREI-MS and NMR analyses.…”

“…The benzoquinazoline core was confirmed by observation of the three aromatic resonance pairs in the range of 8.8–7.5 ppm. The first is two singlets for H-5 and H-10; the second is for H-6 and H-9 in the form of two broad doublets, and the third is two identical broad triplets at around 7.60 and 7.50 ppm for H-7 and H-8, respectively [ 13 , 17 , 23 , 24 ]. The core structure was confirmed from the 12 typical 13 C-resonances, including the most downfield ones at around 161.0 and 156.0 ppm, assignable for C-4 and C-2, respectively.…”

“…White amorphous powder (82%); mp 296 °C; 1 H NMR (700 MHz, DMSO- d 6 ): δ 12.96 (s, 1H, -NH-), 8.69 (s, 1H, H-5), 8.12 (br d, J = 8 Hz, 1H, H-6), 7.93 (br d, J = 8 Hz, 1H, H-9), 7.74 (s, 1H, H-10), 7.62 (br t, J = 7.4 Hz, 1H, H-7), 7.50 (br t, J = 7.4 Hz, 1H, H-8), 4.49 (t, q = 7 Hz, 2H, H-1′), 1.27 (t, J = 7 Hz, 3H, H-2′); 13 C NMR (175 MHz, DMSO- d 6 ): δ 175.4 (C-2), 159.5 (C-4), 136.6 (C-4b,9a), 135.3 (C-5a), 130.0 (C-5), 129.9 (C-6), 129.7 (C-8), 127.7 (C-4a), 126.1 (C-9), 116.0 (C-7), 111.5 (C-10), 41.4 (C-1′), 12.7 (C-2′); HRMS-MS: m / z calcd. for C 14 H 12 N 2 OS (M) •+ 256.0670, found 256.0693 [ 23 , 24 ].…”

Computational insight to design new potential hepatitis C virus NS5B polymerase inhibitors with drug-likeness and pharmacokinetic ADMET parameters predictions

“…Hepatitis C Virus (HCV) is considered a worldwide health problem since it affects over 3% of the population and causes 300,000 fatalities per year [1]. Chronic infection causes high morbidity and mortality in patients, leading to liver cirrhosis, hepatocellular carcinoma, fibrosis, liver cancer, and other HCV-related illnesses [2]. HCV is an encapsulated single-strand linear positively oriented RNA virus belonging to the species Hepacivirus, which belongs to the Flaviviridae family.…”

“…The host ribosomes translate HCV-RNA into a polyprotein, which is then processed by host and viral proteases into ten proteins: three structural proteins (core, E1, and E2), an ion channel (p7), and six non-structural proteins (NS2, NS3, NS4A, NS4B, NS5A, and NS5B) [2]. The virus nucleocapsid is made up of structural proteins, while non-structural proteins are involved in virus development, maturation, and reproduction.…”