title: Synthesis and antiviral activity of beta-carboline derivatives bearing a substituted carbohydrazide at C-3 against poliovirus and herpes simplex virus (HSV-1).
abstract: Several novel 1,3-disubstituted beta-carboline derivatives bearing a substituted carbohydrazide group at C-3 were synthesized and evaluated for their antiviral activity against vaccinal poliovirus (VP) and herpes simplex virus type 1 (HSV-1). The cytotoxicity and selectivity index of the active compounds were also evaluated. Among the synthesized derivatives, compounds 10 and 11 displayed potent activity against both vaccinal poliovirus and HSV-1 virus. Compound 10 presented the highest selectivity index (SI=2446.8) against HSV-1 virus and low cytotoxicity (CC(50)=1150.0+/-67.3 microM). The virus yield inhibition assay showed that compound 10 was able to inhibit HSV-1 plaque formation before and during the virus adsorption. The characteristic small plaque pattern observed in compound-treated cells suggested that compound 10 inhibited viral dissemination to neighboring cells. A computational study for prediction of ADME properties of the novel synthesized beta-carbolines derivatives was performed by determination of lipophilicity, topological polar surface area (TPSA), absorption (% ABS) and simple molecular descriptors, using Lipinski's rule.
authors: Departamento de Química, UEM, Universidade Estadual de Maringá, Avenida Colombo 5790, 87020-900 Maringá, PR, Brazil.
authors: Anelise S
authors: AS
authors: Nazari Formagio
authors: Patricia R
authors: PR
authors: Santos
authors: Karine
authors: K
authors: Zanoli
authors: Tania
authors: T
authors: Ueda-Nakamura
authors: Lilian T
authors: LT
authors: Düsman Tonin
authors: Celso V
authors: CV
authors: Nakamura
authors: Maria Helena
authors: MH
authors: Sarragiotto
mesh_terms: D000818:Animals; D000998:Antiviral Agents / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology*; D002243:Carbolines / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology*; D002522:Chlorocebus aethiops; D006561:Herpes Simplex / Q000188:drug therapy*; D018259:Herpesvirus 1, Human / Q000187:drug effects*; D006801:Humans; D008826:Microbial Sensitivity Tests; D011051:Poliomyelitis / Q000188:drug therapy*; D017955:Poliovirus / Q000187:drug effects*; D014709:Vero Cells
chemical_list: D000998:Antiviral Agents; D002243:Carbolines