Antiviral activity of 4-oxoquinoline-3-carboxamide derivatives against bovine herpesvirus type 5.

BACKGROUND: Bovine herpesvirus type 5 is an important agent of meningoencephalitis in cattle and has been identified in outbreaks of bovine neurological disease in several Brazilian states. In recent years, oxoquinoline derivatives have become an important focus in antiviral drug research. METHODS: The cytotoxicity and anti BoHV-5RJ42/01 activity of a set of synthetic 4-oxoquinoline derivatives 4a-k were assayed on Madin-Darby Bovine Kidney cell and antiviral activity by plaque reduction assay. RESULTS: The most promising substance (4h) exhibited CC50 and EC50 values of 1,239 µM ±5.5 and 6.0 µM ±1.5, respectively, with an SI =206. Two other compounds 4j (CC50 = 35 µM ±2 and EC50 = 24 µM ±7.0) and 4k (CC50= 55 µM ±2 and EC50 = 24 µM ±5.1) presented similar inhibitory profile and selectivity indexes of 1.4 and 2.9, respectively. The results of the time-of-addition studies revealed expressive reduction of virus production (≥80%) in different stages of virus replication cycle except for compound 4h that slightly inhibited virus yield in the first 2 h post infection, but it showed expressive virus inhibition after this time. CONCLUSIONS: All three compounds slightly interact with the virus on the virucidal assay and they are not able to block virus attachment and penetration. Antiviral effect of oxoquinoline 4h was more prominent than acyclovir which leads us to suggest compound 4h as a promising molecule for further anti-BoHV-5 drug design.

Synthesis and antitumor evaluation of hybrids of 5,8-dioxo-5,8-dihydroisoquinoline-4-carboxylates and carbohydrates.

AIM: Cancer has emerged as a growing public health problem in many parts of the world. METHODOLOGY: We describe the synthesis of a series of carbohydrate-based isoquinoline-5,8-diones through the 1,4-addition reaction between 5,8-dioxo-5,8-dihydroisoquinoline and aminocarbohydrates. Halogenated quinones were also synthesized. Their inhibitory effects on the proliferation of human cancer cell lines were studied. RESULTS & CONCLUSION: The most promising compound, derived from isoquinoline-5,8-dione, containing ribofuranosidyl ring, was selectively active in vitro against H1299 cancer cells, with 1.7-fold higher activity than that of vinorelbine tartrate. This result suggests that the glycoconjugate in question may constitute a valuable lead compound to design and synthesize a more active and less toxic derivative with respect to the development of a new antitumor substance.