Saqallah, Fadi Ghassan Mohammed
(2023)
Theobromine-Based Synthetic Derivatives As Potential Inhibitors Of Dengue Virus Ii Serine Protease.
PhD thesis, Perpustakaan Hamzah Sendut.
Abstract
Dengue is an RNA viral disease that is spread across tropical and subtropical
urbanised districts. Up to June 2022, more than 17,497 cases of dengue infections have
been reported in Malaysia since the beginning of the year, which is considered an
increment of 57.6% compared to the first six months of 2021. Moreover, up to date,
there is no licensed drug treatment for the management of dengue infections. Dengue
virus (DENV) uses the NS2B/NS3 protease to cleave its polyprotein throughout the
virus’s replication and life cycle. Hence, inhibiting the viral protease can suppress the
replication of DENV. Previously, some unpublished data by our group showed that
Theobroma cacao inhibited the DENV2 protease. Theobromine is a naturally
occurring alkaloid commonly found in Theobroma cacao. Theobromine has a purine
chemical scaffold which resembles that of 19 famous antivirals, which are either
commercially available or under clinical investigations, including acyclovir.
Moreover, only a few studies have reported the synthesis of theobromine and its
derivatives, but to date, none have been related to antiviral agents. In this study, a
group of 137 theobromine-based hybrid molecules were designed by conjugating
theobromine (at position °1; the secondary amine) with other commercially available
chemical entities and compounds.
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