title: Structure based molecular design, synthesis and biological evaluation of α-pyrone analogs as anti-HSV agent.
abstract: Several options for treating Herpes Simplex Virus type 1 and type 2 are available. However, non-specific inhibition and drug resistance warrants the discovery of new anti-herpetic compounds with better therapeutic profile or different mode of action. The non-nucleoside inhibitors of HSV DNA polymerase target the site that is less important for the binding of a natural nucleoside or nucleoside inhibitors. In the present study, we have explored the possibility to find a new lead molecule based on α-pyrone analogs as non-nucleoside inhibitors using structure based modeling approach. The designed molecules were synthesized and evaluated for anti-HSV activity using MTT assay. The compound 5h with EC(50) 7.4μg/ml and CC(50) 52.5μg/ml was moderately active against HSV when compared to acyclovir. A plaque reduction assay was also carried out and results reveal that 5h is more effective against HSV-1 with better selective index of 12.8 than against HSV-2 (SI=3.6). The synthesized compounds were also evaluated for anti-HIV activity, but none were active.
authors.affiliation: Department of Applied Chemistry, Birla Institute of Technology, Mesra, Ranchi 835215, India.
authors.forename: Srinivas
authors.initials: S
authors.lastname: Karampuri
authors.forename: Paromita
authors.initials: P
authors.lastname: Bag
authors.forename: Sabina
authors.initials: S
authors.lastname: Yasmin
authors.forename: Devendra Kumar
authors.initials: DK
authors.lastname: Chouhan
authors.forename: Chandralata
authors.initials: C
authors.lastname: Bal
authors.forename: Debashis
authors.initials: D
authors.lastname: Mitra
authors.forename: Debprasad
authors.initials: D
authors.lastname: Chattopadhyay
authors.forename: Ashoke
authors.initials: A
authors.lastname: Sharon
mesh_terms: D000998:Antiviral Agents / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology*; D004305:Dose-Response Relationship, Drug; D015195:Drug Design; D018259:Herpesvirus 1, Human / Q000187:drug effects*; D018258:Herpesvirus 2, Human / Q000187:drug effects*; D008826:Microbial Sensitivity Tests; D008958:Models, Molecular; D015394:Molecular Structure; D011753:Pyrones / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology*; D013329:Structure-Activity Relationship
chemical_list: D000998:Antiviral Agents; D011753:Pyrones