Inhibition of human adenoviruses by 1-(2′-hydroxy-5′-methoxybenzylidene)amino-3-hydroxyguanidine tosylate

Abstract

Antiviral activities of four Schiff bases of aminohydroxyguanidine, designated ML1, ML4, ATL14 and LK11, were tested against human adenovirus types 5 and 8 (Ad5 and Ad8) in A549 cells by plaque reduction and virus yield reduction methods. Compound (ML1 1-(2'-hydroxy-5'-methoxybenzylidene)amino-3-hydroxyguanidine tosylate gave the best therapeutic indices (TC50/IC50) of 27.2 and 17.8 for Ad5 and Ad8, respectively. Pretreatment of cells with ML1 did not affect the adsorption nor the penetration of virus. Ultrastructure studies showed that only the drug treated infected cells had unidentified irregular shaped electron dense structures that might be drug altered viral macromolecules that were not assembled into complete infectious virus particles. Since these compounds have metal chelating properties, their antiviral activity may involve the early IA (EIA) gene which encodes a viral protein of 289 amino acid which has a zinc finger moiety that is required for its transactivation activity.

Intramolecular hydrogen bonding in o‐hydroxyaryl Schiff bases

“…The imine formation mechanism that actively participates in physiological tempering of the human immune system has attracted conciderable attention from immunologists in the last decade. [21][22][23][24][25][26][27][28][29] The series of N-hydroxy-N 1 -aminoguanidines can serve as an example of aldimines with antitumor and antiviral properties [30][31][32][33][34][35] and those fighting or slowing leukaemia cell growth. 36,37 Also, ketimines with a bulky naphthyl or phenyl substituent at the imine group influence the central nervous system, regulating its activity in a special way.…”

Development of HIV protease inhibitors: A survey

“…A new generation of protease inhibitors with higher potency, improved pharmacokinetic profile, fewer drug interactions, better tolerability and convenient dosing schedule will be highly desirable. Development of new classes of agents aimed at other targets such as HIVintegrase, zinc-finger [76] and ribonucleotide reductase [77] is also warranted, and may produce additional armament in the fight against AIDS. Combination therapy of viral infection with multiple drugs acting by different mechanisms may offer several advantages over monotherapy: (1) potential synergistic effect; (2) possible reduction of dosages and side-effects; (3) reduction of the chance of drug resistance, for example, if a single drug has a 1% chance of producing resistance viral particles, the combination of three different drugs will reduce the chance to 1/10 6 during the same period of time.…”

Schiff Bases as Important Class of Pharmacological Agents

“…13) is one of the few antiviral drugs which affect the inhibition of vasoconstriction induced anaphylactic shock (adenovirus type Ad5 and Ad8). Their activity is related to the coordination properties that prevent decoding of genes responsible for the synthesis of amino acids of the virus [52].…”

“…Chemical structure of oxphaman[52].Schiff Bases as Important Class of Pharmacological Agents997 compounds in…”