Browsing by Author "Gunaratna, Medha J."

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Design, synthesis and evaluation of 3-hydroxy quinazolinone derivatives as urease inhibitors against Helicobacter pylori
(Institute of Chemistry Ceylon, 2020) Ruhunage, S. A.; Udukala, Dinusha N.; Gunaratna, Medha J.
Gastritis is a common virulent disease found in the present world. The main pathogen which can cause gastritis is Helicobacter pylori and the infection from this bacterium in the upper gastrointestinal tract can lead to ulcers and gastric carcinoma. The activity and the growth of this bacteria in gastric juice of the stomach are favored by the bacterial urease enzyme. Therefore, urease enzyme inhibition plays a significant role in reducing the survival of the pathogen in the stomach. Apart from that, due to bacterial resistance and toxicity problems associated with the current drugs available against H. pylori, discovery of novel urease inhibitors is highly demanded. In this study, two 3-hydroxyquinazolinone derivatives were synthesized using anthranilic acid. Synthesized compounds were characterized using NMR spectroscopy. Urease inhibitory action of the synthesized compounds was measured by a colorimetric method called the Berthelot method. The amount of ammonia produced from urea due to urease enzyme activity was determined by this method. Inhibition of urease resulted low levels of ammonia produced and therefore low levels of absorbance. Among the two compounds, 3-hydroxy- 2-phenyl-4(3H)-quinazolinone exhibited high levels of inhibition at low concentrations with an IC50 value of 19.95 ± 1.03 μg/mL. This experiment was supported by a computational approach with the use of Gold score software for docking analysis and Chimera 1.9 for visualization of the docked molecules. The computational scores resulted in which 3-hydroxy-2-phenyl-4(3H)-quinazolinone was shown to be a better urease inhibitor compared to 3-hydroxy-2-methyl-4(3H)-quinazolinone by providing higher binding affinity and better Gold score values. Both experimental and computational results favored 3-hydroxy-2-phenyl-4(3H)-quinazolinone as a preferable urease inhibitor.
Design, synthesis, and evaluation of 2, 3-disubstituted quinazolin-4(3H)-one derivatives as urease inhibitors against Helicobacter pylori
(Institute of Chemistry Ceylon, 2020) Madujith, E. A. D. N.; Gunaratna, Medha J.; Udukala, Dinusha N.
Helicobacter pylori is a pathogenic bacterium that causes ulcers and inflammations in the stomach lining. This bacterium produces urease enzyme which catalyzes the hydrolysis of urea in the stomach to carbon dioxide gas and ammonia. Resultant ammonia neutralizes stomach acid and helps H. pylori to survive and colonize in the acidic environment of the stomach. Therefore, inhibition of urease is a good strategy for controlling Helicobacter pylori. In this study, a series of 2,3-disubstituted quinazolinone derivatives was designed and their binding affinities to urease enzyme were studied using molecular docking. Auto dock GOLD 5.0.3 and Discovery studio v16.1.0.15 software were used for the computational docking study. In the synthesis, anthranilic acid was reacted with benzoyl chloride followed by dehydration to form a benzoxazinone intermediate. Subsequent addition of an amine to the benzoxazinone intermediate provided fused quinazolinone, named 3-amino-2- phenylquinazolin-4(3H)-one (NE-05). An improved method was developed for the synthesis of NE-05 in solvent-free conditions. Schiff bases (NE-06, 07, 08) were synthesized by the reaction of NE-05 with aldehydes benzaldehyde, p-hydroxybenzaldehyde and formaldehyde respectively. The structures of the synthesized derivatives were confirmed using IR and NMR spectroscopy. In vitro, urease inhibitory activity of the synthesized compounds was evaluated using modified Berthelot’s spectrophotometric method. Among the synthesized compounds, NE-05, NE-06, NE-07 and NE-08 showed an inhibitory effect of more than 50%, and among them, NE-06 and NE-07 are the two most promising compounds
Detailed evaluation of methylated and acetylated products of cinnamon leaf oil against Aedes aegypti
(Institute of Chemistry Ceylon Adamantane House, Rajagiriya, Sri Lanka., 2020) Medagedara, H. K.; Paranagama, P. A.; Gunaratna, Medha J.
Aedes aegypti is a known vector of several viruses including Yellow fever, Dengue, Chikungunya and Zika virus. Two potential Aedes aegypti mosquito repellents; methyl eugenol and acetyl eugenol were semi-synthesized using eugenol extracted from cinnamon leaf, which is the main constituent in cinnamon leaf as well as in other plant leaf extracts like maduruthala and clove oil. Methyl eugenol was semi-synthesized using methyl iodide as a methylation precursor and acetyl eugenol was semi-synthesized using acetic anhydride, triethylamine base and catalytic amount of DMAP. Synthesis reactions were monitored using TLC and products were purified using flash silica columns. Formations of desired products were confirmed using GC-MS analysis. A diluted series (0.6-8 mg/ mL) was prepared for these semi-synthesized compounds and for the cinnamon leaf extract using ethanol and tested separately for their mosquito repellency using arm-in-cage tests followed by standard WHO methods. Experiments were performed on twenty volunteers in triplicates. Effective dose (ED99) for each repellent was calculated using beta regression analysis. Current study suggests that all compounds tested were effective mosquito repellents. Their ED99 varied as; cinnamon leaf extract (5.80) > methyl eugenol (5.41) > acetyl eugenol (5.13). Acetyl eugenol could be a potential safe repellent as its ED99 was achieved at a lower concentration and due to the absence of any side effects on skin when applied. Both maduruthala and clove oil contained significant contents of eugenol and clove oil had slight amounts of acetyl eugenol which could be extracted to synthesize repellent compounds or use directly in future.
Evaluation of phytochemical composition and biological activities of ethanol extract of bark of Dialium ovoideum Thwaites
(Chathurangani,D. A. Upeka and Udukala,Dinusha N. and Gunaratna,Medha J., 20240352316, English, Journal article, India, doi:10.5958/0975-6892.2024.00037.8, 0975-4261 0975-6892, 16, (2), New Delhi, Medicinal Plants - International Journal of Phytomedicines and Related Industries, (350–358), Society for Conservation and Resource Development of Medicinal Plants, Evaluation of phytochemical composition and biological activities of ethanol extract of bark of Dialium ovoideum thwaites., (2024), 2024) Chathurangani, D.A. Upeka; Udukala, Dinusha N.; Gunaratna, Medha J.
The present study aimed to investigate the biological activities of the ethanol extract of the bark of Dialium ovoideum Thwaites (DOEB), which is an endemic plant of Sri Lanka with various medicinal values. A powdered bark sample was subjected to soxhlet extraction using ethanol followed by solvent evaporation to obtain the bark extract. The phytochemical screening performed on DOEB revealed the presence of phenols, flavonoids, tannins, saponins, terpenoids and steroids. The total phenolic and flavonoid contents of the DOEB were measured as 233.4±22.7 mg GAE/g and 198.1±24.5 mg QE/g, respectively. The antioxidant activity of DOEB showed an EC 50 of 68.5±6.3 μg/mL for the DPPH free radical scavenging assay and a significant (p<0.05) reductive potential compared to the ascorbic acid for the FRAP assay with a percentage reductive potential ranging from 5.7±0.8 to 79.2±2.2% across concentrations of 12.5 to 400 μg/mL. The modified L-DOPA method revealed the anti-tyrosinase activity of DOEB which is expressed as the IC50 of 1298.3±36.2 μg/mL. The human red blood cell stabilization assay by heat hemolysis resulted in an IC 50 of 425.7±9.3 μg/mL. The agar-well diffusion assay was conducted to assess the anti-microbial activities against the Staphylococus aureus, Escherichia coli, Klebsiella pneumoniae bacterial strains and the fungus, Candida albicans. The results exhibited that DOEB inhibited the growth of all three bacteria and fungi in different concentrations. Functional groups analysis of DOEB by FT-IR spectroscopy revealed the presence of alcohols, carboxylic acids, alkanes, alkenes, aliphatic esters, carbonyl and aromatic compounds. This study showed that DOEB has promising bioactivities based on the assays conducted which has a high potential to isolate bioactive compounds. Hence, DOEB may be employed as a prospective candidate in the food and pharmaceutical industries.
Evaluation of phytochemical composition and biological activities of ethanol extract of bark of Dialium ovoideum Thwaites
(Journal of Environmental Accounting and Management, 2023) Chathurangani, D.A. Upeka; Udukala, Dinusha N.; Gunaratna, Medha J.
Antioxidants have been discovered to play an important unction in protecting the body rom damage caused by reactive ree radicals via interacting with ree radicals, chelating, and serving as oxygen scavengers. Dialium ovoideum thwaites, an endemic plant in Sri Lanka, which is locally identified as Gal Siyambala. Leaves o D. ovoideum thwaites have been reported to possess antioxidant properties. Hence, this study aimed to investigate the phytochemical profile and evaluate the antioxidant properties o the ethanol extract o the bark o D. ovoideum thwaites. The extract was prepared using the Soxhlet extraction method and it was subjected to phytochemical screening using standard procedures. The gravimetric method was utilized to conduct the quantitative analysis o flavonoids, tannins, and saponins. Folin-Ciocalteau assay was used to determine the total phenolic content. DPPH radical scavenging and erric-reducing power assays were used to determine the antioxidant properties. The results o qualitative phytochemical screening showed the presence o phenols, flavonoids, saponins, steroids and tannins. In quantitative analysis, the phytochemical constituents indicated 10.7% (w/w) o flavonoids, 1.1% (w/w) o tannins and 0.9% (w/w) o saponins. The total phenolic content was 233.4±22.7 mg gallic acid equivalent/g extract while the IC50 value or the DPPH assaywas 68.5±6.3 µg/mL which is comparable to ascorbic acid (32.0±2.1 µg/mL). The reducing potential o the extract showed that it possesses a significant (p<0.05) reductive potential as compared with the ascorbic acid standard. Results revealed that the ethanol extract o the bark o D. ovoideum thwaites exhibits antioxidant properties which are positively correlated with its total phenolic content.
Evaluation of phytochemical composition and novel bioactivities from fresh fruit of Garcinia quaesita Pierre
(Indian Journal.com, 2024) Ekanayaka, K.S.J.; Gunaratna, Medha J.
The fruit rind of Garcinia quaesita Pierre is known as a condiment with therapeutic potential, including antioxidant, antihyperglycemic, and anti-proliferative effects. However, there has been a lack of in-depth investigation into its phytochemical composition and its activities related to anti-inflammatory, and anti-tyrosinase activities. In this study a 1:1 ethanol : water extract of fresh fruit of Garcinia quaesita was used. Preliminary phytochemical screening revealed the presence of numerous bioactive compounds, including alkaloids, polyphenols, flavonoids, glycosides, coumarins, anthraquinones, steroids, terpenoids, saponin, and xanthoproteins. The Total Phenolic Content (TPC) of the fruit extract of G. quaesita was 3053.25 ± 30.07 μg GAE g−1, and Total Flavonoid Content (TFC) was 443.19 ± 4.76 μg CE g−1. The extract exhibited moderate antioxidant activity (IC50 238.14 ± 0.68 μg mL−1) compared to ascorbic acid. In anti-inflammatory assays, compared to O-acetyl salicylic acid, the extract showed notably higher inhibitory effects against egg albumin denaturation and heat-induced hemolysis with lower IC50 values of 762.49 ± 1.70 μg mL−1 and 617.66 ± 1.75 ìg mL−1 respectively. Correlation analysis highlighted strong positive correlations between TPC and antioxidant (r=0.801) and anti-inflammatory (r=0.725 and r=0.605) activities, highlighting the role of TPC. At 4 mg mL−1, the fruit extract of Garcinia quaesita Pierre exhibited lower inhibitory activity of tyrosinase with an IC50 value of 3.31 ± 0.04 mg mL−1, than kojic acid. Additionally, the SPF value at 2 mg mL−1 was 15, indicating moderate UV protection. In conclusion, this study suggests the potential use of fresh G. quaesita fruit extract for functional foods and cosmetics, owing to its rich phytochemical composition and bioactivities, especially in antioxidative and anti-inflammatory domains.
Evaluation of phytochemical composition and novel bioactivities from fresh fruit of Garcinia quaesita Pierre
(2024) Ekanayaka, K.S.J.; Gunaratna, Medha J.; Nusfa, M.L.F.
The fruit rind of Garcinia quaesita Pierre is known as a condiment with therapeutic potential, including antioxidant, antihyperglycemic, and anti-proliferative effects. However, there has been a lack of in-depth investigation into its phytochemical composition and its activities related to anti-inflammatory, and anti-tyrosinase activities. In this study a 1:1 ethanol : water extract of fresh fruit of Garcinia quaesita was used. Preliminary phytochemical screening revealed the presence of numerous bioactive compounds, including alkaloids, polyphenols, flavonoids, glycosides, coumarins, anthraquinones, steroids, terpenoids, saponin, and xanthoproteins. The Total Phenolic Content (TPC) of the fruit extract of G. quaesita was 3053.25 ± 30.07 μg GAE g−1, and Total Flavonoid Content (TFC) was 443.19 ± 4.76 μg CE g−1. The extract exhibited moderate antioxidant activity (IC50 238.14 ± 0.68 μg mL−1) compared to ascorbic acid. In anti-inflammatory assays, compared to O-acetyl salicylic acid, the extract showed notably higher inhibitory effects against egg albumin denaturation and heat- induced hemolysis with lower IC50 values of 762.49 ± 1.70 μg mL−1 and 617.66 ± 1.75 ìg mL−1 respectively. Correlation analysis highlighted strong positive correlations between TPC and antioxidant (r=0.801) and anti-inflammatory (r=0.725 and r=0.605) activities, highlighting the role of TPC. At 4 mg mL−1, the fruit extract of Garcinia quaesita Pierre exhibited lower inhibitory activity of tyrosinase with an IC50 value of 3.31 ± 0.04 mg mL−1, than kojic acid. Additionally, the SPF value at 2 mg mL−1 was 15, indicating moderate UV protection. In conclusion, this study suggests the potential use of fresh G. quaesita fruit extract for functional foods and cosmetics, owing to its rich phytochemical composition and bioactivities, especially in antioxidative and anti-inflammatory domains.
The OSMAC effect on the production of secondary metabolites by the endolichenic fungus, Curvularia trifolii
(Institute of Chemistry Ceylon Adamantane House, Rajagiriya, Sri Lanka., 2020) Lekamwasam, C. J.; Paranagama, P. A.; Gunaratna, Medha J.
Fungi are a very diverse group of organisms that can produce a vast number of pharmacologically active secondary metabolites. Fungi also have the ability to produce numerous secondary metabolites from a single strain. In this study, the One Strain Many Compounds (OSMAC) approach was used to observe the biosynthetic potential of endolichenic fungus, Curvularia trifolii isolated from Usnea sp. in Sri Lanka. Under the OSMAC approach, the variation of the metabolic profile of the fungus when cultured in different culture media was investigated. Culturing in Potato Dextrose Broth (PDB) medium resulted in the elution of two peaks in High- Performance Liquid Chromatographic (HPLC) study while four major peaks resulted from Yeast Potato Dextrose Broth (YPDB) medium cultures. Five major peaks eluted from Oatmeal extract broth (OEB) medium cultures and two major peaks from Rice-Yeast Broth (RYB) medium cultures. The bioactivities of crude extracts from each culture media were investigated using antioxidant, antibacterial, and anti-inflammatory assays and analyzed using Graph Pad Prism software. The crude extract of OEB showed a comparatively high antioxidant activity with ABTS radical scavenging assay with an IC50 value of 0.501 ± 0.036 mg mL-1 while the crude extract of YPDB showed a comparatively high anti-inflammatory activity with human red blood cell stabilization assay with an IC50 value of 0.151 ± 0.026 mg mL-1. The crude extract of RYB showed the highest antibacterial activity against Escherichia coli, Staphylococcus aureus, and Bacillus subtilis bacterial strains upon analysis using agar-well diffusion method. The study confirms the variation of metabolic products and associated bioactivities of Curvularia trifolii with the variation of its culture medium.
Synthesis, evaluation and structure activity relationship study of 2-phenyl-3H-quinazolinone derivatives as urease inhibitors against Helicobacter pylori
(Institute of Chemistry Ceylon, 2020) Alwis, Y. Vindula; Gunaratna, Medha J.; Udukala, Dinusha N.
Urease is a nickel containing metalloenzyme, which catalyzes the hydrolysis of urea into ammonia and carbon dioxide. It is an essential enzyme for Helicobacter pylori, which is a bacterium that has an ability to colonize upon the gastric wall, causing gastric ulcers and development of adenocarcinoma. By inhibition of urease, their growth and colonization can be ceased and therefore can be used as a pharmaceutical agent against H. pylori. This research was focused on the synthesis of the derivatives of 2-phenyl-3H-quinazolin-4-one and on the evaluation of their urease inhibitory action. Six derivatives of 2-phenyl-3H-quinazolin-4-one were synthesized in good yields (64%- 88%) by the oxidative cyclo-condensation of 2-aminobenzamide with benzaldehydes (namely 4-hydroxybenzaldehyde, 4-methoxybenzaldehyde, 4-chlorobenzaldehyde, 4-cyanobenzaldehyde, 4-hydroxy-3-methoxybenzaldehyde and benzaldehyde) in a refluxing aqueous solution of FeCl3. The structures of synthesized analogues were confirmed using spectroscopic techniques such as 1H-NMR, 13C-NMR and FT-IR and by the determination of the melting points of compounds which were previously reported in literature. The urease inhibitory activities of synthesized compounds were quantified using an assay developed from Berthelot’s reaction. Urease required for the assay was extracted from the germinated seeds of Macrotyloma uniflorum (Horse-gram) and thiourea was used as the positive control. The synthesized derivatives of 2-phenyl-3H-quinazolin-4-one showed moderate to high potencies in the urease inhibition, as the IC50 values of all compounds except 2-(4-cyanophenyl)-3H-quinazolin-4-one and 2-(4-chlorophenyl)-3H-quinazolin-4-one, were less than that of the positive control (i.e., 0.80 mg/mL). When a Structure Activity Relationship (SAR) study was carried out by building up a linear free-energy correlation diagram, the exponential of the potencies of synthesized compounds were found to be directly proportional to the substituent constants, where the potency increased with the electron donating nature of the substituent groups. Thus, 2-phenyl-3H-quinazolin-4-one derivatives can be further optimized as “hits” in the drug discovery against H. pylori.
Urease inhibitory activity of the leaves and fruits of Trichosanthes cucumerina Linn.
(Institute of Chemistry Ceylon, 2020) Dharmajeewa, H. D. O. P.; Gunaratna, Medha J.; Udukala, Dinusha N.
Helicobacter pylori is a bacterium found in stomach which secretes bacterial urease, a major virulent factor to cause peptic ulcers. Hence, numerous studies have been carried out to investigate urease inhibitory activity of herbal extracts to treat peptic ulcers through the elimination of colonization of Helicobacter pylori. The plant of interest in this research was Trichosanthes cucumerina Linn. which is referred by the name ‘dummella’ in Sinhala. Leaves of this plant are currently being used to treat peptic ulcers in traditional medicinal methods and have been strongly suggested for research. This study was focused on exploring the urease inhibitory activity of leaves and fruits of Trichosanthes cucumerina Linn. Following the extractions prepared using hexane, ethyl acetate, methanol and water, urease inhibitory activity of each extract was evaluated using a colorimetric assay developed from Berthelot’s reaction. Urease enzyme was extracted from Macrotyloma uniflorum (Horse gram/“Kollu”) and thiourea was used as the standard inhibitor. Among the five samples which showed the urease inhibitory property, the lowest IC50 value of 1.134±0.008 mg/mL was obtained for the ethyl acetate extract of the fruit of Trichosanthes cucumerina Linn., thereby showed the highest urease inhibitory activity. The water extract of leaves of the plant showed the highest total phenolic content (0.104±0.003 mg GAE g-1) and total flavonoid content (0.027±0.005 mg of quercetin equivalents/g of dried weight. These results suggest a strong indication to use this plant parts in the treatment against the main causative of peptic ulcers and further research on such natural origins can be used to design and develop novel drugs with lesser toxicity.