Ghee Tan | University of Hawaii at Hilo (original) (raw)

Papers by Ghee Tan

Anticancer activity against Human lung carcinoma (LU-1) and Human prostrate carcinoma (LnCap) alo... more Anticancer activity against Human lung carcinoma (LU-1) and Human prostrate carcinoma (LnCap) along with antimicrobial and antioxidant activity on DPPH ((1,1)-diphenyl-2-picrylhydrazyl) and Hydrogen peroxide radicals scavenging activity and the contents of total phenolic and flavonoids were assessed in methanol extract of Lespedeza bicolor. The highest content of total phenolic content was detected in the arial part of Lespedeza bicolor (0.5-1.7 mg gallic acid equiv./g), while the highest content of total flavonoids was found in the aerial part of Lespedeza bicolor (0.102-0.148 mg/g D/W). Lespedeza bicolor arial parts and root extract showed IC 50 value of 12.5μg/ml and 50μg/ml against human lung carcinoma (LU-1) whereas, ≤ 12.5 μg/ml and 12μg/ml were calculated against Human prostrate carcinoma (LnCap) cell line. MIC value of 20-35 μg ml −1 has been observed gainst Aspergillus fumigates, Aspergillus niger, Fusarium solani and Mucor sp in comparision with 1-2.5μg/ml of Terbinafine used as a standard fungicide. MIC value of 20 μg/ml and 35 μg ml −1 of Lespedeza bicolor arial parts and root extract against bacterial pathogen Klebsiella pneumonia and 20-50 μg ml −1 against Enterococcus has been measured. DPPH radical scavenging activity of Lespedeza bicolor with IC 50 values of ≤ 50 μg/ml and ≤ 200 μg ml −1 was observed whereas, hydrogen peroxide scavenging activity with IC 50 values of ≤ 25 μg/ml for arial parts and ≤ 50 μg ml −1 for the root extract of Lespedeza bicolor has been shown with galllic acid (R2= 0.819) and ascorbic acid (R2= 0.728). These data suggested that the methanolic extract of Lespedeza bicolor could be potential candidates for natural antioxidants and anticancer.

ACS Combinatorial Science, Feb 12, 2018

Herein we report the antibacterial structure-activity relationships of cyclic hexapeptide wollami... more Herein we report the antibacterial structure-activity relationships of cyclic hexapeptide wollamide analogs derived from solid-phase library synthesis. Wollamide B, a cyclic hexapeptide natural product, has been previously found to have activity against Mycobacterium bovis. To further evaluate its antimycobacterial/antibacterial potential, 27 peptides including wollamides A/B, and desotamide B, were synthesized and subsequently tested against a panel of clinically significant bacterial pathogens. Biological evaluation revealed that the cyclic scaffold, amide functionality in position I, tryptophan residue in position V, and the original stereochemistry pattern of the core scaffold were key for antituberculosis and/or antibacterial activity. In addition, against M. tuberculosis and Gram-positive bacteria, residues in position II and/or VI greatly impacted antibacterial activity and selectivity. Wollamides A (3) and B (2) along with their corresponding II (l-Leu) analog 10 retained the most promising antituberculosis activity, with the lowest minimum inhibitory concentration (MIC) against virulent M. tuberculosis H37Rv (MIC = 1.56 μg/mL), as well as desirable selectivity indices (>100). Importantly, the antimicrobial activities of wollamides A and B do not result from disruption of the bacterial membrane, warranting further investigation into their mechanism of action.

Fucoidan is a group of sulfated polysaccharides isolated from marine algae. Fucoidan exhibits a v... more Fucoidan is a group of sulfated polysaccharides isolated from marine algae. Fucoidan exhibits a variety of biological activities which are related to their chemically distinct sulfated fucose backbone. The structures of select fucoidans vary by species, and the structure and bioactivity remains unclear. The fucoidan of Padina sp., Asparagopsis taxiformus, and Nishime Kombu were extracted using four different methods using water at different temperatures. Method 2 gave the highest yield of fucoidan by 1 H NMR analysis, whereas method 4 yielded FCSPs with anti-cancer activities. The crude fucoidan of Padina sp. was further purified using ion-exchange chromatography, resulting in the highest yield of fucoidan at 2.5 M NaCl. Cell viability was determined using sulforhodamine B (SRB) assay in five cancer cells (LNCap, PC-3, MCF-7, Caco-2, and LU-1). Both standard and Kombu-extracted fucoidan showed no effects on prostate (LNCaP and PC-3), and breast (MCF-7) cancer cells, but inhibited the growth of colon (Caco-2) and lung (LU-1) cancer cells by 43-74% at concentrations in the range of 50-400 µg/mL. These crude FCSPs also exhibited antioxidant activity. The FRAP values of Nishime Kombu, U-Fn, and Fucoidan Force, were 586.44 ± 107 µM/mg extract, 2922.38 ± 981 µM/mg, and 4212.03 ± 745 µM/mg, respectively.

This study was designed to examine the anticancer, antioxidant and antimicrobial activities of th... more This study was designed to examine the anticancer, antioxidant and antimicrobial activities of the essential oil from Lycopus lucidus Turcz. var. hirtus Regel. The essential oil treatment to six human cancer cell lines resulted in a dose-dependent inhibition of cell growth. The cytotoxicity of the essential oil on liver carcinoma and breast cancer cell lines was significantly stronger than on other cell lines. The essential oil can induce apoptosis of the liver carcinoma cell line Bel-7402 and decrease the intracellular GSH level. The antioxidant effect of the essential oil was evaluated by using 2,2-diphenyl-1-picrylhydrazyl (DPPH) and hydroxyl radical (OH Å) scavenging assays. The essential oil exhibited moderate antioxidant activity. The antimicrobial activity of the essential oil was evaluated against eight microorganisms using the disc diffusion and broth microdilution methods. The essential oil also showed moderate antimicrobial activity. These suggest that the essential oil could hold a good potential for use in the pharmaceutical industry.

ChemMedChem, Sep 17, 2012

International Journal of Molecular Sciences, Mar 30, 2021

This article is an open access article distributed under the terms and conditions of the Creative... more This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY

Experimental Parasitology

In an extension of the authors` work in the sulfonic acid polymer area they have evaluated the re... more In an extension of the authors` work in the sulfonic acid polymer area they have evaluated the reverse transcriptase (RT) inhibitory activity of several varying molecular weight aromatic and aliphatic derivatives. All the polymers possess anti-HIV activity at doses that are non-toxic to the host cells and act by inhibiting viral adsorption. In the RT assay, poly(4-styrenesulfonic acid) exhibited highly potent inhibition with IC{sub 50} values of 0.0008 {mu}M and 0.0007 {mu}M for HIV-1 and HIV-2 RT respectively. The discovery of the anti-RT potential of these derivatives provides the impetus to investigate additional intervention strategies that are coupled with the facilitated cellular penetration of these agents.

Pharmaceutical Biology, 2011

Context: Whether natural product drug discovery programs should rely on wild plants collected "ra... more Context: Whether natural product drug discovery programs should rely on wild plants collected "randomly" from the natural environment, or whether they should also include plants collected on the basis of use in traditional medicine remains an open question. Objective: This study analyzes whether plants with ethnomedical uses from Vietnam and Laos have a higher hit rate in bioassay testing than plants collected from a national park in Vietnam with the goal of maximizing taxonomic diversity ("random" collection). Materials and Methods: All plants were extracted and subjected to bioassay in the same laboratories. Results of assays of plant collections and plant parts (samples) were scored as active or inactive based on whether any extracts had a positive result in a bioassay. Contingency tables were analyzed using chi-square statistics. Results: Random collections had a higher hit rate than ethnomedical collections, but for samples, ethnomedical plants were more likely to be active. Ethnomedical collections and samples had higher hit rates for tuberculosis, while samples, but not collections, had a higher hit rate for malaria. Little evidence was found to support an advantage for ethnomedical plants in HIV, chemoprevention and cancer bioassays. Plants whose ethnomedical uses directly correlated to a bioassay did not have a significantly higher hit rate than random plants. Discussion: Plants with ethnomedical uses generally had a higher rate of activity in some drug discovery bioassays, but the assays did not directly confirm specific uses. 3 Conclusion: Ethnomedical uses may contribute to a higher rate of activity in drug discovery screening.

Journal of Natural Products, Jan 9, 2014

A new lignan, vitexkarinol (1), as well as a known lignan, neopaulownin (2), a known chalcone, 3-... more A new lignan, vitexkarinol (1), as well as a known lignan, neopaulownin (2), a known chalcone, 3-(4-hydroxyphenyl)-1-(2,4,6-trimethoxyphenyl)-2-propen-1-one (3), two known dehydroflavones, tsugafolin (4) and alpinetin (5), two known dipeptides, aurantiamide and aurantiamide acetate, a known sesquiterpene, vemopolyanthofuran, and five known carotenoid metabolites, vomifoliol, dihydrovomifoliol, dehydrovomifoliol, loliolide and isololiolide, were isolated from the leaves and twigs of Vitex leptobotrys through bioassay-guided fractionation. The chalcone (3) was found to inhibit HIV-1 replication by 77% at 15.9 µM, and the two dehydroflavones (4 and 5) showed weak anti-HIV activity with IC 50 values of 118 and 130 µM, respectively, while being devoid of cytotoxicity at 150 µM. A chlorophyll-enriched fraction of V. leptobotrys, containing pheophorbide a, was found to inhibit the replication of HIV-1 by 80% at a concentration of 10 µg/mL. Compounds 1 and 3 were further selected to be evaluated against 21 viral targets available at NIAID

Cancer Research

We recently reported the cellular signal-modulating properties of altersolanol B (AB), a minor fu... more We recently reported the cellular signal-modulating properties of altersolanol B (AB), a minor fungal tetrahydroanthraquinone (THAQ) metabolite, in the estrogen receptor positive (ER+) human breast adenocarcinoma cell lines, MCF-7 and T47D. MCF-7 (IC50 5.5 µM) and T47D (IC50 8.8 µM) were observed to be 4- and 2.4-fold more sensitive to the antiproliferative effects of AB, respectively, compared to MDA-MB-231 (triple-negative, IC50 21.3 µM). AB disrupted both AKT and ERK1/2 signaling leading to intrinsic apoptosis in MCF-7. The clinical limitations of multi-agent combination therapy that targets multiple pathways in cancer may potentially be circumvented by using a single molecule, such as AB, that inhibits both AKT and ERK1/2 signaling. The THAQ pharmacophore, with its disrupted conjugated ring system and relative redox inactivity, may possess greater mechanistic advantage against ER+ breast cancer when compared to the fully conjugated ring systems of the anthracyclines (doxorubicin...

Chemico-Biological Interactions, 2022

The present study focused on the apoptosis-inducing effects and cellular signal-modulating proper... more The present study focused on the apoptosis-inducing effects and cellular signal-modulating properties of altersolanol B (AB), a minor fungal tetrahydroanthraquinone (THAQ) metabolite, in the estrogen receptor positive (ER+) human breast adenocarcinoma cell line, MCF-7. AB demonstrated approximately 4-fold greater antiproliferative activity in ER+ MCF-7 cells (IC50 5.5 μM) compared to the ER-negative (triple-negative) MDA-MB-231 (IC50 21.3 μM). The viability of normal breast fibrocystic epithelial cells, MCF-10A, was unaffected. AB induced intrinsic apoptosis in MCF-7 cells; it triggered the activation of caspase 9 and poly (ADP-ribose) polymerase (PARP), upregulated the expression of pro-apoptotic Bax, and downregulated the expression of antiapoptotic Bcl-2. AB induced cell cycle arrest at G0/G1, as indicated by the downregulation of key checkpoint proteins operating at the G0/G1 phase of the cell cycle (cyclin D1, CDK4 and CDK2). The observed increase in p21Waf1/Cip1 and p53 expression may facilitate cell cycle arrest, and the subsequent induction of apoptosis. AB lacked significant effects on intracellular ROS levels, while it down-regulated nuclear factor erythroid 2-related factor 2 (Nrf2), and the Nrf2-dependent antioxidant enzyme, heme oxygenase-1. The compound disrupted AKT signaling through the downregulation of phospho-AKT and phospho-FOXO1, and the upregulation of PTEN, a phosphatase and tumor suppressor that negatively regulates the PI3K/AKT pathway. AB also disrupted the phosphorylation of AKT-controlled eukaryotic translation initiation factor, 4E-BP1, and GSK-3β, both of which are aberrantly regulated in human cancer. The AB-dependent downregulation of NF-κB was corroborated by the inhibition of TNFα-induced NF-κB activity as monitored in a luciferase reporter. The NF-κB inhibitory activity of AB was 3-fold more potent than that of the standard inhibitor, N-p-Tosyl-L phenylalanine chloromethyl ketone. In addition to reducing the pro-survival effects of NF-кB, the inhibition of AKT phosphorylation by AB may also lead to FOXO1-mediated growth arrest and apoptosis. AB upregulated the expression of phospho-MKK4 and phosphop38, and downregulated the expression of phospho-MEK1/2 and phospho-ERK1/2 indicating opposing effects on the two important oncogenic signaling cascades that are aberrantly activated in many cancers. AB disrupted both the AKT and ERK1/2 signaling pathways leading to apoptosis in ER+ MCF-7 cells through mitochondria-associated mechanisms coupled with the potent inhibition of NF-кB activation. The clinical limitations of multi-agent combination therapy that targets multiple pathways in cancer may potentially be circumvented by using a single molecule, such as AB, that inhibits both AKT and ERK1/2 signaling. Our preliminary study suggested that the THAQ pharmacophore, with its disrupted conjugated ring system and relative redox inactivity, may possess greater mechanistic advantage against ER+ breast cancer when compared to the fully conjugated ring systems of the anthraquinone that possess intrinsic redox activity and DNA interacting ability. This study supports the continued investigation of THAQs as lead molecules in anticancer drug discovery and development.

International Journal of Molecular Sciences, 2021

A molecular docking approach was employed to evaluate the binding affinity of six triterpenes, na... more A molecular docking approach was employed to evaluate the binding affinity of six triterpenes, namely epifriedelanol, friedelin, α-amyrin, α-amyrin acetate, β-amyrin acetate, and bauerenyl acetate, towards the cannabinoid type 1 receptor (CB1). Molecular docking studies showed that friedelin, α-amyrin, and epifriedelanol had the strongest binding affinity towards CB1. Molecular dynamics simulation studies revealed that friedelin and α-amyrin engaged in stable non-bonding interactions by binding to a pocket close to the active site on the surface of the CB1 target protein. The studied triterpenes showed a good capacity to penetrate the blood–brain barrier. These results help to provide some evidence to justify, at least in part, the previously reported antinociceptive and sedative properties of Vernonia patula.

International Journal of Phytomedicine, 2012

Concerning anticancer evaluation of methanolic extract of Suaeda fruticosa arial parts demonstrat... more Concerning anticancer evaluation of methanolic extract of Suaeda fruticosa arial parts demonstrated the utmost anticancer activity with IC 50 value of 50 μg/ml against human lung carcinoma (LU-1), the same extract displayed a preeminent activity with IC 50 ≥ 50 μg/ml against hormone dependent prostrate carcinoma (LnCaP). The analyzed root extract exhibited IC 50 ≤ 65 μg/ml against hormone dependent prostrate carcinoma (LnCaP) whereas, the same extract demonstrated IC 50 ≤ 55 μg/ml against human lung carcinoma (LU-1). The highest content of total phenolic (0.52-0.67 mg gallic acid equiv./g) and total flavonoids (0.44 mg/g D/W) content was detected in the arial part of Suaeda fruticosa . MIC value of 50-85 μg ml −1 has been observed gainst Aspergillus fumigates, Aspergillus niger, Fusarium solani and Mucor sp in comparision with 1-2.5μg/ml of Terbinafine used as a standard fungicide. MIC value of 80 μg/ml and 35 μg ml −1 of Suaeda fruticosa arial parts and root extract against bacte...

Anticancer research, 2005

Two anthracenone C-glycosides, alvaradoins E and F, isolated from the leaves of Alvaradoa haitien... more Two anthracenone C-glycosides, alvaradoins E and F, isolated from the leaves of Alvaradoa haitiensis Urb. (Simaroubaceae), were found to have potent inhibitory activities with cultured cancer cells. Using the in vivo hollow fiber model, these compounds demonstrated significant growth inhibition at the i.p. site when tested with KB, LNCaP, and Col2 cells. To determine if these anthracenone C-glycosides mediated anticancer activity through an apoptotic pathway, a series of assays were performed with the 10S isomeric compound, alvaradoin E. With a DAPI assay, treatment of LNCaP cells with alvaradoin E at concentrations of 0.4, 2, 10, or 50 microM for 24 or 48 h showed chromatin condensation, a morphological characteristic of apoptosis. Mitochondrial membrane potential, analyzed with a DiOC6 uptake assay, showed that treatment of LNCaP cells with 0.07, 0.14, 0.28, 0.56, 0.86, and 1.12 microM alvaradoin E for 12 h caused dose-dependent membrane depolarization, another indication of early...

Journal of Microbiology and Biotechnology

Population ageing poses a variety of problems that challenge public health worldwide. Extensive r... more Population ageing poses a variety of problems that challenge public health worldwide. Extensive research has demonstrated that the number of adults aged 60 years and older will increase more rapidly in developing countries than in developed countries [1]. Ageing has been recognized as the first and foremost risk factor for noncommunicable diseases (NCDs), including tumors, heart diseases, hypertension, and diabetes [2]. The World Health Organization has concluded that deaths of over-60s caused by NCDs total over twice the number of those below 60 years of age. Cancer is regarded as a typical NCD, and represents one of the most serious health conditions on a global scale,

Anticancer activity against Human lung carcinoma (LU-1) and Human prostrate carcinoma (LnCap) alo... more Anticancer activity against Human lung carcinoma (LU-1) and Human prostrate carcinoma (LnCap) along with antimicrobial and antioxidant activity on DPPH ((1,1)-diphenyl-2-picrylhydrazyl) and Hydrogen peroxide radicals scavenging activity and the contents of total phenolic and flavonoids were assessed in methanol extract of Lespedeza bicolor. The highest content of total phenolic content was detected in the arial part of Lespedeza bicolor (0.5-1.7 mg gallic acid equiv./g), while the highest content of total flavonoids was found in the aerial part of Lespedeza bicolor (0.102-0.148 mg/g D/W). Lespedeza bicolor arial parts and root extract showed IC 50 value of 12.5μg/ml and 50μg/ml against human lung carcinoma (LU-1) whereas, ≤ 12.5 μg/ml and 12μg/ml were calculated against Human prostrate carcinoma (LnCap) cell line. MIC value of 20-35 μg ml −1 has been observed gainst Aspergillus fumigates, Aspergillus niger, Fusarium solani and Mucor sp in comparision with 1-2.5μg/ml of Terbinafine used as a standard fungicide. MIC value of 20 μg/ml and 35 μg ml −1 of Lespedeza bicolor arial parts and root extract against bacterial pathogen Klebsiella pneumonia and 20-50 μg ml −1 against Enterococcus has been measured. DPPH radical scavenging activity of Lespedeza bicolor with IC 50 values of ≤ 50 μg/ml and ≤ 200 μg ml −1 was observed whereas, hydrogen peroxide scavenging activity with IC 50 values of ≤ 25 μg/ml for arial parts and ≤ 50 μg ml −1 for the root extract of Lespedeza bicolor has been shown with galllic acid (R2= 0.819) and ascorbic acid (R2= 0.728). These data suggested that the methanolic extract of Lespedeza bicolor could be potential candidates for natural antioxidants and anticancer.

ACS Combinatorial Science, Feb 12, 2018

Herein we report the antibacterial structure-activity relationships of cyclic hexapeptide wollami... more Herein we report the antibacterial structure-activity relationships of cyclic hexapeptide wollamide analogs derived from solid-phase library synthesis. Wollamide B, a cyclic hexapeptide natural product, has been previously found to have activity against Mycobacterium bovis. To further evaluate its antimycobacterial/antibacterial potential, 27 peptides including wollamides A/B, and desotamide B, were synthesized and subsequently tested against a panel of clinically significant bacterial pathogens. Biological evaluation revealed that the cyclic scaffold, amide functionality in position I, tryptophan residue in position V, and the original stereochemistry pattern of the core scaffold were key for antituberculosis and/or antibacterial activity. In addition, against M. tuberculosis and Gram-positive bacteria, residues in position II and/or VI greatly impacted antibacterial activity and selectivity. Wollamides A (3) and B (2) along with their corresponding II (l-Leu) analog 10 retained the most promising antituberculosis activity, with the lowest minimum inhibitory concentration (MIC) against virulent M. tuberculosis H37Rv (MIC = 1.56 μg/mL), as well as desirable selectivity indices (>100). Importantly, the antimicrobial activities of wollamides A and B do not result from disruption of the bacterial membrane, warranting further investigation into their mechanism of action.

Fucoidan is a group of sulfated polysaccharides isolated from marine algae. Fucoidan exhibits a v... more Fucoidan is a group of sulfated polysaccharides isolated from marine algae. Fucoidan exhibits a variety of biological activities which are related to their chemically distinct sulfated fucose backbone. The structures of select fucoidans vary by species, and the structure and bioactivity remains unclear. The fucoidan of Padina sp., Asparagopsis taxiformus, and Nishime Kombu were extracted using four different methods using water at different temperatures. Method 2 gave the highest yield of fucoidan by 1 H NMR analysis, whereas method 4 yielded FCSPs with anti-cancer activities. The crude fucoidan of Padina sp. was further purified using ion-exchange chromatography, resulting in the highest yield of fucoidan at 2.5 M NaCl. Cell viability was determined using sulforhodamine B (SRB) assay in five cancer cells (LNCap, PC-3, MCF-7, Caco-2, and LU-1). Both standard and Kombu-extracted fucoidan showed no effects on prostate (LNCaP and PC-3), and breast (MCF-7) cancer cells, but inhibited the growth of colon (Caco-2) and lung (LU-1) cancer cells by 43-74% at concentrations in the range of 50-400 µg/mL. These crude FCSPs also exhibited antioxidant activity. The FRAP values of Nishime Kombu, U-Fn, and Fucoidan Force, were 586.44 ± 107 µM/mg extract, 2922.38 ± 981 µM/mg, and 4212.03 ± 745 µM/mg, respectively.

This study was designed to examine the anticancer, antioxidant and antimicrobial activities of th... more This study was designed to examine the anticancer, antioxidant and antimicrobial activities of the essential oil from Lycopus lucidus Turcz. var. hirtus Regel. The essential oil treatment to six human cancer cell lines resulted in a dose-dependent inhibition of cell growth. The cytotoxicity of the essential oil on liver carcinoma and breast cancer cell lines was significantly stronger than on other cell lines. The essential oil can induce apoptosis of the liver carcinoma cell line Bel-7402 and decrease the intracellular GSH level. The antioxidant effect of the essential oil was evaluated by using 2,2-diphenyl-1-picrylhydrazyl (DPPH) and hydroxyl radical (OH Å) scavenging assays. The essential oil exhibited moderate antioxidant activity. The antimicrobial activity of the essential oil was evaluated against eight microorganisms using the disc diffusion and broth microdilution methods. The essential oil also showed moderate antimicrobial activity. These suggest that the essential oil could hold a good potential for use in the pharmaceutical industry.

ChemMedChem, Sep 17, 2012

International Journal of Molecular Sciences, Mar 30, 2021

This article is an open access article distributed under the terms and conditions of the Creative... more This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY

Experimental Parasitology

In an extension of the authors` work in the sulfonic acid polymer area they have evaluated the re... more In an extension of the authors` work in the sulfonic acid polymer area they have evaluated the reverse transcriptase (RT) inhibitory activity of several varying molecular weight aromatic and aliphatic derivatives. All the polymers possess anti-HIV activity at doses that are non-toxic to the host cells and act by inhibiting viral adsorption. In the RT assay, poly(4-styrenesulfonic acid) exhibited highly potent inhibition with IC{sub 50} values of 0.0008 {mu}M and 0.0007 {mu}M for HIV-1 and HIV-2 RT respectively. The discovery of the anti-RT potential of these derivatives provides the impetus to investigate additional intervention strategies that are coupled with the facilitated cellular penetration of these agents.

Pharmaceutical Biology, 2011

Context: Whether natural product drug discovery programs should rely on wild plants collected "ra... more Context: Whether natural product drug discovery programs should rely on wild plants collected "randomly" from the natural environment, or whether they should also include plants collected on the basis of use in traditional medicine remains an open question. Objective: This study analyzes whether plants with ethnomedical uses from Vietnam and Laos have a higher hit rate in bioassay testing than plants collected from a national park in Vietnam with the goal of maximizing taxonomic diversity ("random" collection). Materials and Methods: All plants were extracted and subjected to bioassay in the same laboratories. Results of assays of plant collections and plant parts (samples) were scored as active or inactive based on whether any extracts had a positive result in a bioassay. Contingency tables were analyzed using chi-square statistics. Results: Random collections had a higher hit rate than ethnomedical collections, but for samples, ethnomedical plants were more likely to be active. Ethnomedical collections and samples had higher hit rates for tuberculosis, while samples, but not collections, had a higher hit rate for malaria. Little evidence was found to support an advantage for ethnomedical plants in HIV, chemoprevention and cancer bioassays. Plants whose ethnomedical uses directly correlated to a bioassay did not have a significantly higher hit rate than random plants. Discussion: Plants with ethnomedical uses generally had a higher rate of activity in some drug discovery bioassays, but the assays did not directly confirm specific uses. 3 Conclusion: Ethnomedical uses may contribute to a higher rate of activity in drug discovery screening.

Journal of Natural Products, Jan 9, 2014

A new lignan, vitexkarinol (1), as well as a known lignan, neopaulownin (2), a known chalcone, 3-... more A new lignan, vitexkarinol (1), as well as a known lignan, neopaulownin (2), a known chalcone, 3-(4-hydroxyphenyl)-1-(2,4,6-trimethoxyphenyl)-2-propen-1-one (3), two known dehydroflavones, tsugafolin (4) and alpinetin (5), two known dipeptides, aurantiamide and aurantiamide acetate, a known sesquiterpene, vemopolyanthofuran, and five known carotenoid metabolites, vomifoliol, dihydrovomifoliol, dehydrovomifoliol, loliolide and isololiolide, were isolated from the leaves and twigs of Vitex leptobotrys through bioassay-guided fractionation. The chalcone (3) was found to inhibit HIV-1 replication by 77% at 15.9 µM, and the two dehydroflavones (4 and 5) showed weak anti-HIV activity with IC 50 values of 118 and 130 µM, respectively, while being devoid of cytotoxicity at 150 µM. A chlorophyll-enriched fraction of V. leptobotrys, containing pheophorbide a, was found to inhibit the replication of HIV-1 by 80% at a concentration of 10 µg/mL. Compounds 1 and 3 were further selected to be evaluated against 21 viral targets available at NIAID

Cancer Research

We recently reported the cellular signal-modulating properties of altersolanol B (AB), a minor fu... more We recently reported the cellular signal-modulating properties of altersolanol B (AB), a minor fungal tetrahydroanthraquinone (THAQ) metabolite, in the estrogen receptor positive (ER+) human breast adenocarcinoma cell lines, MCF-7 and T47D. MCF-7 (IC50 5.5 µM) and T47D (IC50 8.8 µM) were observed to be 4- and 2.4-fold more sensitive to the antiproliferative effects of AB, respectively, compared to MDA-MB-231 (triple-negative, IC50 21.3 µM). AB disrupted both AKT and ERK1/2 signaling leading to intrinsic apoptosis in MCF-7. The clinical limitations of multi-agent combination therapy that targets multiple pathways in cancer may potentially be circumvented by using a single molecule, such as AB, that inhibits both AKT and ERK1/2 signaling. The THAQ pharmacophore, with its disrupted conjugated ring system and relative redox inactivity, may possess greater mechanistic advantage against ER+ breast cancer when compared to the fully conjugated ring systems of the anthracyclines (doxorubicin...

Chemico-Biological Interactions, 2022

The present study focused on the apoptosis-inducing effects and cellular signal-modulating proper... more The present study focused on the apoptosis-inducing effects and cellular signal-modulating properties of altersolanol B (AB), a minor fungal tetrahydroanthraquinone (THAQ) metabolite, in the estrogen receptor positive (ER+) human breast adenocarcinoma cell line, MCF-7. AB demonstrated approximately 4-fold greater antiproliferative activity in ER+ MCF-7 cells (IC50 5.5 μM) compared to the ER-negative (triple-negative) MDA-MB-231 (IC50 21.3 μM). The viability of normal breast fibrocystic epithelial cells, MCF-10A, was unaffected. AB induced intrinsic apoptosis in MCF-7 cells; it triggered the activation of caspase 9 and poly (ADP-ribose) polymerase (PARP), upregulated the expression of pro-apoptotic Bax, and downregulated the expression of antiapoptotic Bcl-2. AB induced cell cycle arrest at G0/G1, as indicated by the downregulation of key checkpoint proteins operating at the G0/G1 phase of the cell cycle (cyclin D1, CDK4 and CDK2). The observed increase in p21Waf1/Cip1 and p53 expression may facilitate cell cycle arrest, and the subsequent induction of apoptosis. AB lacked significant effects on intracellular ROS levels, while it down-regulated nuclear factor erythroid 2-related factor 2 (Nrf2), and the Nrf2-dependent antioxidant enzyme, heme oxygenase-1. The compound disrupted AKT signaling through the downregulation of phospho-AKT and phospho-FOXO1, and the upregulation of PTEN, a phosphatase and tumor suppressor that negatively regulates the PI3K/AKT pathway. AB also disrupted the phosphorylation of AKT-controlled eukaryotic translation initiation factor, 4E-BP1, and GSK-3β, both of which are aberrantly regulated in human cancer. The AB-dependent downregulation of NF-κB was corroborated by the inhibition of TNFα-induced NF-κB activity as monitored in a luciferase reporter. The NF-κB inhibitory activity of AB was 3-fold more potent than that of the standard inhibitor, N-p-Tosyl-L phenylalanine chloromethyl ketone. In addition to reducing the pro-survival effects of NF-кB, the inhibition of AKT phosphorylation by AB may also lead to FOXO1-mediated growth arrest and apoptosis. AB upregulated the expression of phospho-MKK4 and phosphop38, and downregulated the expression of phospho-MEK1/2 and phospho-ERK1/2 indicating opposing effects on the two important oncogenic signaling cascades that are aberrantly activated in many cancers. AB disrupted both the AKT and ERK1/2 signaling pathways leading to apoptosis in ER+ MCF-7 cells through mitochondria-associated mechanisms coupled with the potent inhibition of NF-кB activation. The clinical limitations of multi-agent combination therapy that targets multiple pathways in cancer may potentially be circumvented by using a single molecule, such as AB, that inhibits both AKT and ERK1/2 signaling. Our preliminary study suggested that the THAQ pharmacophore, with its disrupted conjugated ring system and relative redox inactivity, may possess greater mechanistic advantage against ER+ breast cancer when compared to the fully conjugated ring systems of the anthraquinone that possess intrinsic redox activity and DNA interacting ability. This study supports the continued investigation of THAQs as lead molecules in anticancer drug discovery and development.

International Journal of Molecular Sciences, 2021

A molecular docking approach was employed to evaluate the binding affinity of six triterpenes, na... more A molecular docking approach was employed to evaluate the binding affinity of six triterpenes, namely epifriedelanol, friedelin, α-amyrin, α-amyrin acetate, β-amyrin acetate, and bauerenyl acetate, towards the cannabinoid type 1 receptor (CB1). Molecular docking studies showed that friedelin, α-amyrin, and epifriedelanol had the strongest binding affinity towards CB1. Molecular dynamics simulation studies revealed that friedelin and α-amyrin engaged in stable non-bonding interactions by binding to a pocket close to the active site on the surface of the CB1 target protein. The studied triterpenes showed a good capacity to penetrate the blood–brain barrier. These results help to provide some evidence to justify, at least in part, the previously reported antinociceptive and sedative properties of Vernonia patula.

International Journal of Phytomedicine, 2012

Concerning anticancer evaluation of methanolic extract of Suaeda fruticosa arial parts demonstrat... more Concerning anticancer evaluation of methanolic extract of Suaeda fruticosa arial parts demonstrated the utmost anticancer activity with IC 50 value of 50 μg/ml against human lung carcinoma (LU-1), the same extract displayed a preeminent activity with IC 50 ≥ 50 μg/ml against hormone dependent prostrate carcinoma (LnCaP). The analyzed root extract exhibited IC 50 ≤ 65 μg/ml against hormone dependent prostrate carcinoma (LnCaP) whereas, the same extract demonstrated IC 50 ≤ 55 μg/ml against human lung carcinoma (LU-1). The highest content of total phenolic (0.52-0.67 mg gallic acid equiv./g) and total flavonoids (0.44 mg/g D/W) content was detected in the arial part of Suaeda fruticosa . MIC value of 50-85 μg ml −1 has been observed gainst Aspergillus fumigates, Aspergillus niger, Fusarium solani and Mucor sp in comparision with 1-2.5μg/ml of Terbinafine used as a standard fungicide. MIC value of 80 μg/ml and 35 μg ml −1 of Suaeda fruticosa arial parts and root extract against bacte...

Anticancer research, 2005

Two anthracenone C-glycosides, alvaradoins E and F, isolated from the leaves of Alvaradoa haitien... more Two anthracenone C-glycosides, alvaradoins E and F, isolated from the leaves of Alvaradoa haitiensis Urb. (Simaroubaceae), were found to have potent inhibitory activities with cultured cancer cells. Using the in vivo hollow fiber model, these compounds demonstrated significant growth inhibition at the i.p. site when tested with KB, LNCaP, and Col2 cells. To determine if these anthracenone C-glycosides mediated anticancer activity through an apoptotic pathway, a series of assays were performed with the 10S isomeric compound, alvaradoin E. With a DAPI assay, treatment of LNCaP cells with alvaradoin E at concentrations of 0.4, 2, 10, or 50 microM for 24 or 48 h showed chromatin condensation, a morphological characteristic of apoptosis. Mitochondrial membrane potential, analyzed with a DiOC6 uptake assay, showed that treatment of LNCaP cells with 0.07, 0.14, 0.28, 0.56, 0.86, and 1.12 microM alvaradoin E for 12 h caused dose-dependent membrane depolarization, another indication of early...

Journal of Microbiology and Biotechnology

Population ageing poses a variety of problems that challenge public health worldwide. Extensive r... more Population ageing poses a variety of problems that challenge public health worldwide. Extensive research has demonstrated that the number of adults aged 60 years and older will increase more rapidly in developing countries than in developed countries [1]. Ageing has been recognized as the first and foremost risk factor for noncommunicable diseases (NCDs), including tumors, heart diseases, hypertension, and diabetes [2]. The World Health Organization has concluded that deaths of over-60s caused by NCDs total over twice the number of those below 60 years of age. Cancer is regarded as a typical NCD, and represents one of the most serious health conditions on a global scale,