Susan P. Manly
University of Mississippi
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Featured researches published by Susan P. Manly.
Antimicrobial Agents and Chemotherapy | 2008
Xing-Cong Li; Melissa R. Jacob; Shabana I. Khan; M. Khalid Ashfaq; K. Suresh Babu; Ameeta K. Agarwal; Hala N. ElSohly; Susan P. Manly; Alice M. Clark
ABSTRACT Our continuing effort in antifungal natural product discovery has led to the identification of five 6-acetylenic acids with chain lengths from C16 to C20: 6-hexadecynoic acid (compound 1), 6-heptadecynoic acid (compound 2), 6-octadecynoic acid (compound 3), 6-nonadecynoic acid (compound 4), and 6-icosynoic acid (compound 5) from the plant Sommera sabiceoides. Compounds 2 and 5 represent newly isolated fatty acids. The five acetylenic acids were evaluated for their in vitro antifungal activities against Candida albicans, Candida glabrata, Candida krusei, Candida tropicalis, Candida parapsilosis, Cryptococcus neoformans, Aspergillus fumigatus, Aspergillus flavus, Aspergillus niger, Trichophyton mentagrophytes, and Trichophyton rubrum by comparison with the positive control drugs amphotericin B, fluconazole, ketoconazole, caspofungin, terbinafine, and undecylenic acid. The compounds showed various degrees of antifungal activity against the 21 tested strains. Compound 4 was the most active, in particular against the dermatophytes T. mentagrophytes and T. rubrum and the opportunistic pathogens C. albicans and A. fumigatus, with MICs comparable to several control drugs. Inclusion of two commercially available acetylenic acids, 9-octadecynoic acid (compound 6) and 5,8,11,14-eicosatetraynoic acid (compound 7), in the in vitro antifungal testing further demonstrated that the antifungal activities of the acetylenic acids were associated with their chain lengths and positional triple bonds. In vitro toxicity testing against mammalian cell lines indicated that compounds 1 to 5 were not toxic at concentrations up to 32 μM. Furthermore, compounds 3 and 4 did not produce obvious toxic effects in mice at a dose of 34 μmol/kg of body weight when administered intraperitoneally. Taking into account the low in vitro and in vivo toxicities and significant antifungal potencies, these 6-acetylenic acids may be excellent leads for further preclinical studies.
Journal of Natural Products | 2013
Jiangtao Gao; Mohamed M. Radwan; Francisco León; Olivia R. Dale; Afeef S. Husni; Yunshan Wu; Shari L. Lupien; Xiaoning Wang; Susan P. Manly; Robert A. Hill; Frank M. Dugan; Horace G. Cutler; Stephen J. Cutler
Bioassay-guided fractionation of a fungus Neocosmospora sp. (UM-031509) resulted in the isolation of three new resorcylic acid lactones, neocosmosin A (2), neocosmosin B (3), and neocosmosin C (4). Three known resorcylic acid lactones, monocillin IV (1), monocillin II (5), and radicicol (6), were also isolated and identified. The structures of these compounds were established on the basis of extensive 1D and 2D NMR spectroscopic analysis, mass spectrometric (ESIMS) data, and X-ray crystallography. Compounds 4-6 show good binding affinity for the human opioid receptors. These findings have important implications for evaluating the potential psychoactive effects with this class of compounds.
Journal of Natural Products | 2015
Mohamed M. Radwan; Mahmoud A. ElSohly; Abir T. El-Alfy; Safwat A. Ahmed; Desmond Slade; Afeef S. Husni; Susan P. Manly; L. Wilson; Suzanne Seale; Stephen J. Cutler; Samir A. Ross
Seven new naturally occurring hydroxylated cannabinoids (1-7), along with the known cannabiripsol (8), have been isolated from the aerial parts of high-potency Cannabis sativa. The structures of the new compounds were determined by 1D and 2D NMR spectroscopic analysis, GC-MS, and HRESIMS as 8α-hydroxy-Δ(9)-tetrahydrocannabinol (1), 8β-hydroxy-Δ(9)-tetrahydrocannabinol (2), 10α-hydroxy-Δ(8)-tetrahydrocannabinol (3), 10β-hydroxy-Δ(8)-tetrahydrocannabinol (4), 10α-hydroxy-Δ(9,11)-hexahydrocannabinol (5), 9β,10β-epoxyhexahydrocannabinol (6), and 11-acetoxy-Δ(9)-tetrahydrocannabinolic acid A (7). The binding affinity of isolated compounds 1-8, Δ(9)-tetrahydrocannabinol, and Δ(8)-tetrahydrocannabinol toward CB1 and CB2 receptors as well as their behavioral effects in a mouse tetrad assay were studied. The results indicated that compound 3, with the highest affinity to the CB1 receptors, exerted the most potent cannabimimetic-like actions in the tetrad assay, while compound 4 showed partial cannabimimetic actions. Compound 2, on the other hand, displayed a dose-dependent hypolocomotive effect only.
Journal of Natural Products | 2008
Mohamed M. Radwan; Susan P. Manly; Khalid A. El Sayed; Vikram B. Wali; Paul W. Sylvester; Bhushan Awate; Girish V. Shah; Samir A. Ross
Two new diterpenes, sinulodurin A (1) and sinulodurin B (2), along with two known sterols, 24 S-methyl cholesterol and 24-methylene cholesterol, were isolated from the Palau soft coral Sinularia dura. The structures of the new metabolites were determined on the basis of spectroscopic methods and by comparison of NMR data with those of related metabolites. Sinulodurin A (1) and sinulodurin B (2) showed antiproliferative activity against highly malignant +SA mammary epithelial cells with an IC 50 range of 20-30 microM. They also displayed anti-invasive activity against human highly metastatic prostate cancer PC-3M-CT+ cells in the spheroid disaggregation assay. Furthermore, the antimicrobial activities of the isolates were tested.
Molecular Informatics | 2014
Gang Fu; Sheng Liu; Xiaofei Nan; Olivia R. Dale; Zhendong Zhao; Yixin Chen; Dawn Wilkins; Susan P. Manly; Stephen J. Cutler; Robert J. Doerksen
Glycogen synthase kinase‐3 (GSK‐3) is a multifunctional serine/threonine protein kinase which regulates a wide range of cellular processes, involving various signalling pathways. GSK‐3β has emerged as an important therapeutic target for diabetes and Alzheimer’s disease. To identify structurally novel GSK‐3β inhibitors, we performed virtual screening by implementing a combined ligand‐based/structure‐based approach, which included quantitative structure‐activity relationship (QSAR) analysis and docking prediction. To integrate and analyze complex data sets from multiple experimental sources, we drafted and validated a hierarchical QSAR method, which adopts a two‐level structure to take data heterogeneity into account. A collection of 728 GSK‐3 inhibitors with diverse structural scaffolds was obtained from published papers that used different experimental assay protocols. Support vector machines and random forests were implemented with wrapper‐based feature selection algorithms to construct predictive learning models. The best models for each single group of compounds were then used to build the final hierarchical QSAR model, with an overall R2 of 0.752 for the 141 compounds in the test set. The compounds obtained from the virtual screening experiment were tested for GSK‐3β inhibition. The bioassay results confirmed that 2 hit compounds are indeed GSK‐3β inhibitors exhibiting sub‐micromolar inhibitory activity, and therefore validated our combined ligand‐based/structure‐based approach as effective for virtual screening experiments.
Molecular Informatics | 2014
Gang Fu; Prasanna Sivaprakasam; Olivia R. Dale; Susan P. Manly; Stephen J. Cutler; Robert J. Doerksen
Glycogen synthase kinase‐3 (GSK‐3) is a multifunctional serine/threonine protein kinase which is engaged in a variety of signaling pathways, regulating a wide range of cellular processes. GSK‐3β, also known as tau protein kinase I (TPK‐I), is one of the most important kinases implicated in the hyperphosphorylation of tau that leads to neurodegenerative diseases. Hence, GSK‐3β has emerged as an important therapeutic target. To identify compounds that are structurally novel and diverse compared to previously reported ATP‐competitive GSK‐3β inhibitors, we performed virtual screening by implementing a mixed ligand/structure‐based approach, which included pharmacophore modeling, diversity analysis, and ensemble docking. The sensitivities of different docking protocols to induced‐fit effects were explored. An enrichment study was employed to verify the robustness of ensemble docking, using 13 X‐ray structures of GSK‐3β, compared to individual docking in terms of retrieving active compounds from a decoy dataset. A total of 24 structurally diverse compounds obtained from the virtual screening underwent biological validation. The bioassay results showed that 15 out of the 24 hit compounds are indeed GSK‐3β inhibitors, and among them, one compound exhibiting sub‐micromolar inhibitory activity is a reasonable starting point for further optimization.
Journal of Natural Products | 2011
Jiangtao Gao; Francisco León; Mohamed M. Radwan; Olivia R. Dale; Afeef S. Husni; Susan P. Manly; Shari L. Lupien; Xiaoning Wang; Robert A. Hill; Frank M. Dugan; Horace G. Cutler; Stephen J. Cutler
Phytochemistry Letters | 2009
Mohamed M. Radwan; Raquel Rodriguez-Guzman; Susan P. Manly; Melissa R. Jacob; Samir A. Ross
Journal of Natural Products | 2008
Samir A. Ross; Raquel Rodriguez-Guzman; Mohamed M. Radwan; Melissa R. Jacob; Yuanqing Ding; Xing-Cong Li; Daneel Ferreira; Susan P. Manly
Planta Medica | 2012
Olivia R. Dale; G Ma; C Gemelli; Afeef S. Husni; C McCurdy; Ba Avery; Jf Leon; Eb Furr; Susan P. Manly; Stephen J. Cutler