New carbocyclic ribonucleosides with unsaturated groups at the C-2 position of the nucleobase were designed as potential RNA antiviral compounds. The design was based on the expectation that the monophosphates of these compounds would be inhibitors of the enzyme, IMPDH. Appropriate methodologies were developed to achieve the target molecules. Results from the initial in vitro antiviral studies are mentioned. The IMPDH-associated mechanism of the antiviral activity of the most active compound is supported by enzyme inhibition studies.

The role of inosine monophosphate dehydrogenase (IMPDH) at the metabolic branch point of de novo purine nucleotide biosynthesis makes this enzyme an attractive probe for the discovery of antiviral compounds. Introduction of unsaturation at the 2-position of IMP, the natural substrate for IMPDH, produces Michael acceptors at that position, which results in these compounds being inhibitors of IMPDH. Consistent with this mechanism-based molecular design, some of the parent nucleosides exhibited antiviral activity.

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Ficus benjamina l moraceae (weeping fig) is a medicinal plant that has been used to treat biliousness, dysentery, inflammation, liver diseases, bruises, headache, leprosy and syphilis. Chloroform extract of its leaf was investigated for its growth inhibition on Multiple Myeloma cancer cell lines (MM 1S). The raw extract was sample A. Samples B, C, D and E were derived from further separation of sample A by flash chromatography. Samples A and C at 50 μg/mL concentration significantly inhibited the growth of the cells. Very good percentage & significant (P < 0.05) inhibitions of 83.18% and 99.88% were recorded with samples A and C respectively when compared to the control group. The control drug was Bortezomib at a concentration of 1 μM with inhibition of 99.86%. The results show, for the first time, that Ficus benjamina is a good candidate for management & treatment of multiple myeloma cancer.OBJECTIVETo investigate if Ficus benjamina (Fb) could be effective in the treatment of Multiple Myeloma (MM).METHODSCytotoxicity ScreeningThe in vitro cytotoxic activity of test samples was evaluated using the CellTitre‐Glo Assay.Cell cultureThe cells (MM. 1S) were cultured in RPMI‐1640 + 10% Fetal Bovine Serum (FBS) culture medium in 150 cm2 flasks at 37°C in a 5% CO2 atmosphere. Medium was changed every 2 days until cells were confluent. Confluent cells were harvested after treatment with Trypsin‐EDTA. Cells were then plated in 96‐well tissue culture plates at seeding density of 8 × 104 cells/mL so that each well contained 4000 cells in 50 μL of media.Treatment with test samples50 μL of fresh media containing 2X final concentration of test sample with 2% DMSO was added to MM. 1S cell in 50 μL of media already in each well to obtain the final concentration of test sample with 1% DMSO. Treated cells were incubated for 48 hours at 37°C in a 5% CO2 atmosphere. After equilibration at room temperature for 30 minutes, 100 μL of CellTitre‐Glo 2.0 reagent (Promega), the content was mixed by shaking for 2–3 minutes on a shaker & then incubated at room temperature for 10 minutes.The luminescent signal produced was measured using a micro‐plate luminometer (Tecan Infinite M1000 Pro) with 500 ms integration time per well. Experiments were performed in triplicate.Bortezomib at 1 μM was used as positive control.The percent inhibition or decrease in cell viability was calculated using the formula: urn:x-wiley:08926638:fsb2fasebj2018321supplement80439:equation:fsb2fasebj2018321supplement80439-math-0001 (Darci et al., 2015)LO = Luminescence output.Compounds showing ≥ 50% inhibition were further processed for IC50 determination.RPMI = Medium was developed by Moore et al., at Roswell Park Memorial InstituteRESULTSSignificant percentage inhibition (P < 0.05) of growth was recorded for samples A and C at 50 μg/mL concentration although sample gave better result.DISCUSSION/CONCLUSIONBortezomib is an anti‐cancer drug and the first therapeutic proteasome inhibitor to be used in humans (Haberfeld, 2016). Bortezomib lets proteins kill the cancer cells (House, 2014; Takimoto and calvo, 2008). We propose that the samples A and C have similar mechanisms of action.Cheungpasitporn et al in 2015 and other authors have reported gastrointestinal effects, asthenia & other effects from Bortezomib therapy. None of these have been traced to Fb, thus, it is recommended as a good candidate for Multiple Myeloma therapy. According to figure 2, only sample C @ 50 μg/mL showed mild activity against lung cancer cell line. It is safer than BortezomibSupport or Funding InformationFulbright sponsored the trip to Bowie State University from Nigeria and funded all materials used in the extractions from Ficus benjamina.Professor Thomas Kodadek of the Scripps research institute paid for materials used in the cancer testing.This abstract is from the Experimental Biology 2018 Meeting. There is no full text article associated with this abstract published in The FASEB Journal.