Publications

Abstract The azidodeoxythymidine (I) is protected and reduced to give the amino derivative (III) which is coupled with the dimethoxytetrahydrofuran (IV) or the azine (VII) to give the pyrrole derivative (V) and the triazole derivative (IX) respectively.

The title compounds 2-methyl-3-(substituted methylamino)-(3 H )-quinazolin-4-ones were synthesized by condensing the active hydrogen atom of the amino group of 3-amino-2-methyl-(3 H )-quinazolin-4-one with formaldehyde and appropriate amines. Their structures were confirmed by spectral data (IR, 1H-NMR and Mass) and the purity was ascertained by elemental analysis. Investigation of antimicrobial activity of the test compounds was performed by agar dilution method against 7 pathogenic bacteria, 3 pathogenic fungi and antiHIV activity against replication of HIV-1(IIIB) and HIV-2 (ROD) in MT-4 cells. The compounds exhibited significant antibacterial and antifungal activities.

New synthetic path for preparation of NSAID hydroxamic acids 3a-i was developed (benzotriazolic method). Cytostatic and virustatic activity of these compounds was investigated.

The absence of any formally licensed antiadenovirus drugs and the increasing incidence of life-threatening adenovirus infections in immunosuppressed patients warrant the development of effective antiadenovirus compounds. A detailed study was performed on the antiadenovirus activities of several classes of nucleoside and nucleotide analogues in human embryonic lung fibroblast cells. The antiadenovirus activities were evaluated by three methods, viz., evaluating the adenoviral cytopathic effect, monitoring cell viability by a colorimetric assay, and real-time PCR quantitation of viral DNA as a direct parameter for virus replication. The most active and selective compounds were the acyclic nucleoside phosphonate analogues cidofovir, its adenine analogue (S)-9-(3-hydroxy-2-phosphonylmethoxypropyl)adenine [(S)-HPMPA], and the new derivative (S)-2,4-diamino-6-[3-hydroxy-2-(phosphonomethoxy)propoxy]pyrimidine [(S)-HPMPO-DAPy]; the N7-substituted acyclic derivative 2-amino-7-(1,3-dihydroxy-2-propoxymethyl)purine (S-2242); and the 2',3'-dideoxynucleoside analogues zalcitabine and alovudine. No antiadenovirus activity was observed for the antiviral drugs ribavirin, foscarnet, acyclovir, penciclovir, and brivudin, while ganciclovir displayed modest activity. However, in human osteosarcoma cells transfected with herpes simplex virus thymidine kinase, ganciclovir demonstrated highly potent antiadenovirus activity, suggesting that the efficacy of ganciclovir against adenovirus is limited by inefficient phosphorylation in adenovirus-infected cells, rather than by insufficient inhibition at the viral DNA polymerase level. Collectively, our antiviral data show that the adenovirus DNA polymerase exhibits sensitivity to a relatively broad spectrum of inhibitors and should be studied further as an antiviral target in antiadenovirus drug development programs.

An entry from the Cambridge Structural Database, the world’s repository for small molecule crystal structures. The entry contains experimental data from a crystal diffraction study. The deposited dataset for this entry is freely available from the CCDC and typically includes 3D coordinates, cell parameters, space group, experimental conditions and quality measures.

The synthesis of acyclonucleosides derived from thieno[3,2-c] and thieno[2,3-c][1,2,6]thiadiazine 2,2-dioxides was achieved following the silylation method. Lipase-mediated methodology was employed for deprotection of the acyclic moieties. The antiviral effects were determined against a broad spectrum of viruses, including cytomegalovirus (CMV) and varicella zoster virus (VZV). Only minor antiviral activity against VZV was observed for those acyclonucleosides carrying a benzyl group.