Synthesis of Phosphorylated Derivatives of 2', 3'-O-Isopropylidene Adenosine and their In Ovo Antiviral Activity

Author(s): Syed Rasheed, Chamarthi Naga Raju*, Golla Madhava, Chennamsetty Subramanyam, Shaik Thaslim Basha, Avilala Janardhan, Golla Narasimha.

Journal Name: Letters in Drug Design & Discovery

Volume 14 , Issue 5 , 2017

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Abstract:

Introduction: The demand for new antiviral agents is creating all possible approaches towards the development of newantiviral drugs. One of the possible methodologies that can be used for the discovery of such drugs is the screening of novel organophosphorus compounds for antiviral activity.

Objectives: The primary objective of the study was to discover potential new anti-viral agents by phosphorylating ribosyl moiety at 5′ positionof 2′, 3′-O-isopropylidene adenosine nucleoside and evaluation of their in ovo antiviral activity against New castle disease virus and Blue tongue virus.

Methods: The synthesis of phosphorylated derivatives of 2′, 3′-O-isopropylidene adenosine was carried out by reacting 2′, 3′-O-isopropylidene adenosine (I) with 4-nitrophenylphosphorodichloridate (II) to get intermediate (III). Further, it was reacted with various bioactive secondary and primary amines IV(a-k) to obtain the title compounds V(a-k).All the newly synthesized compounds were screened in ovo for their antiviral activity on New Castle Disease Virus, Blue Tongue Virus by Heamagglutination test and Embryonated chicken Egg Method.

Results: All eggs inoculated with the virus control, 1 mg/mL of the title compounds V(a-k) with New Castle Disease Virus. The Survivability of virus cultured eggs were examined by haemagglutination test upto 96 hr. Piperazine ring containing amine compounds exhibited good antiviral activity, remaining compounds exhibited moderate activity. Compounds V(a-k) exhibited 40-100% embryo survivability basing on bioactive amine attached to phosphorus atom. Compounds Ve and Vi showed inhibition of virus up to 96 hr of which is more than standard Isopropylidene adenosine (I). Based on the lesions on the embryo and the percentage of live cells in Blue tongue virus infected BHK 21 cells, compounds Ve and Vi exhibited more antiviral activity than that of the standard nucleoside isopropylidene adenosine (I) whereas, compounds Va, Vb, Vd, Vg and Vh exhibited moderate activity.

Conclusion: The antiviral activity was mainly influenced by fragments attached to phosphorus atom. Compounds Ve and Vi exhibited good antiviral activity towards New Castle disease virus as well as Blue Tongue Virus whereas remaining compounds exhibited moderate activity. The in ovo antiviral activity results of the synthesized compounds provided an additional direction for the structural optimization of the compounds for the development of antiviral drugs with improved selectivity and reduced side effects.

Keywords: 2', 3'-O-isopropylidene adenosine, Phosphorylation, in ovo antiviral activity, NDV, BTV.

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Article Details

VOLUME: 14
ISSUE: 5
Year: 2017
Page: [567 - 572]
Pages: 6
DOI: 10.2174/1570180813666161020112309
Price: $65

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