Citation
Maqsood, Maryam
(2018)
In vitro evaluation of anti-dengue activity of selected synthetic schiff bases and traditional chinese medicinal plants extracts.
Doctoral thesis, Universiti Putra Malaysia.
Abstract
During the last few decades, dengue virus (DENV) has emerged as the major virus spread by mosquito
that can cause life threatening disease. Recently, it has spread to more than a hundred countries
around the globe and still lacks a specific treatable medication. Hospitals provide only supportive
and symptomatic treatment hence the development of a safe and effective antiviral is an
urgent need. To identify new antivirals against DENV, realms of both synthetic compounds
and ethnomedicine were explored.
A library of eighty-five dithiocarbazate (DTC)-derived Schiff bases and their metal complexes
including twelve plant extracts were analyzed in a primary antiviral evaluation. Hits
displaying 50% or more anti-dengue activity were selected and evaluated through foci
forming unit reduction assay, serotype based analysis and real time quantitative RT-PCR based
time-of-addition analysis.
During antiviral evaluation of synthetic compounds, ten anti-dengue compounds were
identified with promising antiviral activity. Secondary evaluation presented two lead Ni
complexes with SI values 86.3 and 80.4. Ni complexes were the strongest contestants and
inhibited all DENV serotypes equally. Lead compounds inhibited against all stages of virus
replication cycle but the activity was strongest during early stages. It was demonstrated in silico
that Ni complexes were binding at domain III of DENV E-glycoprotein involved during early stages of
replication. In conclusion, Schiff bases and their metal complexes are a whole new horizon for
anti- dengue development and can be tudied further to develop safe, effective, stable, and
affordable anti-dengue in future.
Discovery and development of modern medicine relies on long and rigorous clinical trials until
they are available for public use. Meanwhile, new classes of chemical compounds are
being explored for innovative anti-dengue options, Traditional Chinese Medicinal (TCM)
plants are frequently being used by dengue endemic populations as Contemporary and
Alternate Medicine (CAM). These traditional herbs will continue to be an alternative for
dengue treatment as disease burden is rapidly increasing every year. Present study also
evaluated the anti-dengue potential of twelve TCM plant extracts designated as cool herbs
used for the diseases with high fever.
During antiviral evaluation of TCM plants, four anti-dengue plants were identified. Secondary
evaluation proved two lead plants extract Dryopteris crassirhizoma (DC) and Morus alba (MA) with SI
= 4.21 and 4.62 respectively, which inhibited DENV serotypes equally. In general, the plants were
not equally inhibiting against all stages of viral replication cycle. DC was identified as
potential anti-dengue plant which was active at late stages of virus replication. MA was also
inhibiting but the dose was high, however its safety profile was better than DC and the plant was
active at early stages of viral replication. Our research elucidated and identified the
anti-dengue activity of the TCM plants in practice that have been time-tested to reduce
the illness. Similar research can be planned for other traditional anti-dengue practices. The
present times of integrated treatments brings together conventional medicine with safe
and effective complementary medicine. Combined research approaches from different
healthcare disciplines may lead to identification of new therapeutic
options.
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