brivudine and Keratitis--Herpetic

The development of the antiherpetic therapeutical system was remarkable in the last decade. Nucleoside analogs (5-iodine-2-deoxiuridine, citodine-arabinotide, adenine-arabinotide), as well as specific inhibitors of viruses (Zovirax or Acyclovir) are active medicines for both local and wide-spread forms of the herpes virus infection.

Topics: 2-Aminopurine; Acyclovir; Antiviral Agents; Bromodeoxyuridine; Cidofovir; Cytosine; Drug Combinations; Famciclovir; Foscarnet; Ganciclovir; Humans; Idoxuridine; Keratitis, Herpetic; Oligonucleotides; Ophthalmic Solutions; Organophosphonates; Treatment Outcome; Valacyclovir; Valine; Vidarabine

To evaluate the efficacy of four antiviral agents--1% idoxuridine ointment (group 1), 2% trifluorothymidine ointment (group 2), 3% acyclovir ointment (group 3) and 1% bromovinyldeoxyuridine (BVDU) ointment (group 4)--in herpes simplex keratitis.. Randomized double-blinded clinical trial.. Tertiary care institution in New Delhi.. Eighty patients with uncomplicated herpes simplex keratitis of recent onset who had not previously received antiviral treatment.. Cure rate, frequency and severity of side effects.. Cure rates of 60%, 90%, 90% and 95% were obtained in groups 1, 2, 3 and 4 respectively. The average healing time was 13.4, 8.9, 8.5 and 7.5 days respectively. Side effects (follicular conjunctivitis, epithelial keratopathy and stinging) were more frequent in group 1 than in the other groups.. BVDU has a more pronounced therapeutic effect than idoxuridine, trifluorothymidine and acyclovir in uncomplicated epithelial herpetic disease of recent onset that has not previously been treated.

Topics: Acyclovir; Antiviral Agents; Bromodeoxyuridine; Double-Blind Method; Humans; Idoxuridine; Keratitis, Herpetic; Ointments; Treatment Failure; Trifluridine

A number of 5-heteroaromatic-substituted 2'-deoxyuridines were synthesized from 5-iodo-2'-deoxyuridine using tetraorganotin reagents and palladium complexes as catalyst. The palladium-catalyzed cross-coupling reaction between 5-iodo-2'-deoxyuridine and stannylated heteroaromatics was optimized for the synthesis of the 5-thien-3-yl-2'-deoxyuridine and 5-furan-3-yl-2'-deoxyuridine. 5-(5-Iodothien-2-yl)-2'-deoxyuridine was used as starting material for the synthesis of 5-(5-methylthien-2-yl)-2'-deoxyuridine, 5-(5-vinylthien-2-yl)-2'-deoxyuridine, and 5-(5-ethynylthien-2-yl)-2'- deoxyuridine. 5-(5-Nitrothien-2-yl)-2'-deoxyuridine was synthesized using ceric ammonium nitrate as reagent. 5-(Isoxazol-5-yl)-2'-deoxyuridine was synthesized from 5-(3-oxopropyn-1-yl)-2'-deoxyuridine. Finally, 5-(5-chlorothien-2-yl)-beta-D-arabinofuranosyluracil and 5-(5-bromothien-2-yl)-beta-D-arabinofuranosyluracil were obtained by halogenation of 5-thien-2-yl-beta-D-arabinofuranosyluracil. Introduction of an alkyl substituent in the 5-position of the thienyl group of 5-thien-2-yl-2'-deoxyuridine or substitution of the 2-deoxyribofuranose ring by an arabinofuranose moiety gave decreased activity against HSV-1 and VZV replication when compared with the 5"-halogenated-5-thien-2-yl-2'-deoxyuridines. 5-(5-Bromothien-2-yl)-2'-deoxyuridine caused prompt healing of HSV-1 keratitis when administered as eye drops (0.2%) to rabbits.

Topics: Animals; Antiviral Agents; Cell Line; Cell Survival; Deoxyuridine; Herpes Simplex; Herpesvirus 3, Human; Humans; Keratitis, Herpetic; Mice; Organotin Compounds; Palladium; Rabbits; Simplexvirus; Structure-Activity Relationship; Thiophenes; Virus Replication

The phosphonylmethoxyalkyl derivatives HPMPA [(S)-9-(3-hydroxy-2-phosphonylmethoxypropyl)adenine], HPMPC [(S)-1-(3-hydroxy-2-phosphonylmethoxypropyl)cytosine] and PMEA [9-(2-phosphonylmethoxyethyl)adenine] were evaluated as 0.2% eyedrops for their efficacy in the treatment of experimental herpes simplex virus type 1 (HSV-1) keratitis in the rabbit model. BVDU 0.2% eyedrops were used as the reference treatment. HPMPA, HPMPC, PMEA and BVDU eyedrops showed a rapid and highly significant healing effect (P less than 0.005) on keratitis caused by TK+ HSV-1 (McIntyre strain) when compared with placebo eyedrops, whereas BVDU treatment did not affect the course of TK- HSV-1 (VMW-1837) keratitis. HPMPA and HPMPC treatment again caused a highly significant healing (P less than 0.005, compared with placebo eyedrops). Although PMEA eyedrops were less effective than HPMPA or HPMPC eyedrops, the effect of PMEA eyedrops was significantly (P less than 0.05) different from the effect of either BVDU or placebo eyedrops.

Topics: Adenine; Animals; Antiviral Agents; Bromodeoxyuridine; Cidofovir; Cytosine; Hempa; Keratitis, Herpetic; Ophthalmic Solutions; Organophosphonates; Organophosphorus Compounds; Rabbits; Simplexvirus; Thymidine Kinase

A new acyclic adenosine analogue, (S)-9-(3-hydroxy-2-phosphonylmethoxypropyl)adenine [(S)-HPMPA], was evaluated for its efficacy in the topical treatment of experimental keratitis caused by the thymidine kinase-positive (TK+) and thymidine kinase-deficient (TK-) herpes simplex virus type 1 (HSV-1) strains. In the treatment of TK+ HSV-1 keratitis, 0.2% (S)-HPMPA eyedrops were as effective as the reference compounds, 0.2% (E)-5-(2-bromovinyl)-2'-deoxyuridine (BVDU) and 0.2% 5-(2-chloroethyl)-2'-deoxy-uridine (CEDU) eyedrops. The three compounds produced a statistically significant healing effect, as compared with placebo eyedrops. In the treatment of keratitis caused by the TK- HSV-1 strain, 0.2%BVDU and 0.2% CEDU eyedrops did not differ from placebo eyedrops, whereas 0.2% (S)-HPMPA eyedrops exerted a highly significant healing effect.

Topics: Adenine; Administration, Topical; Animals; Antiviral Agents; Bromodeoxyuridine; Deoxyuridine; Herpesvirus 1, Human; Keratitis, Herpetic; Ophthalmic Solutions; Organophosphonates; Organophosphorus Compounds; Rabbits; Thymidine Kinase