Harrison College of Pharmacy

Current Funding

Unravelling the mechanism of acaí BDS-anticancer drug interaction: A preliminary approach
Funder: National Institutes of Health (NIH) through National Center for Complementary and Integrative Health (NCCIH) and Office of Dietary Supplements (ODS), Grant number: R15AT011047
Date: 2021-2024
Role: Principal Investigator
Total Cost: $440,590.00

Evaluation of the potential of Ashwagandha extracts to produce CYP-mediated drug interactions
Funder: National Institutes of Health (NIH) through National Center for Complementary and Integrative Health (NCCIH) and Office of Dietary Supplements (ODS), Grant number: R03AT011501
Date: 2021-2023
Role: Co-Investigator
Total Cost: $148,960

Laboratory Personnel

Graduate Students

• Kabre Heck
• Kelli McDonald
• Zarna Atul Raichura

Undergraduate Students

• Madeline Kunze
• Zalaya Haynes
• Lauren Fogel
• Catherine Dennis
• Rinbam Kromtit
• Meredith Almy

Former Undergraduate Students

• Keila Adams
• Lauren Walters
• Swati Baskiyar
• Madison Patrick
• Quennetta Baldwin

External Links

• Pubmed Publications
• ORCID Profile
• Google Scholar Profile

Research Interests

Application of mass spectrometry to enzyme kinetics and ligand-enzyme interactions
My research team has proved the relevance of the use of mass spectrometry detection for biological assays and kinetic studies of natural products. The findings from these papers [3, 4, 5, 9, 10, 14, 19] have shown the advantages of using mass spectrometry to directly measure the enzyme inhibitory activity over using other detectors which require additional reagents and coupled enzymes and to establish the kinetic profile of inhibitors. Another important feature is that these assays are designed to identify the types of ligand-enzyme interactions and binding sites.

Mass spectrometry-based natural products drug discovery
My laboratory has addressed the importance of screening and identification of bioactive natural products from plants, marine organisms, and endophytic fungi against Plasmodium falciparum thioredoxin reductase (PfTrxR) and Mycobacterium tuberculosis shikimate kinase (MtSK) enzymes, drug targets for malaria and tuberculosis, respectively [11, 12, 17, 18, 20]. LC-MS based structure elucidation of new and known natural products in complex mixtures has been performed extensively in this research program.

Quality and safety assessment of botanical dietary supplements
We have been working on the development of LC-MS and NMR-based methods for quality control of botanical dietary supplements during the last 14 years at Auburn University. Based on the expertise developed, we published on the LC-MS and NMR extract chemical fingerprinting and profiling and metabolomic studies of plant ingredients and botanical dietary supplements [8, 13, 16]. Additionally, we have developed LC-MS methods for the identification and quantitation of bioactive or analytical markers and identification of adulterants, and qNMR-based quantitative analysis of natural products in plant materials and botanical dietary supplements [7, 13, 15].

In terms of safety, we are currently studying Euterpe oleracea Mart. (açaí) and Withania somnifera (Linn.) Dunal (Ashwagandha) for botanical-drug interactions. Açaí is a botanical commonly used among cancer patients [6]. Recently, we found evidence that açaí extracts interfere with the liver metabolizing CYP3A4 enzyme suggesting potential for pharmacokinetic interactions [1, 2]. The study of the definitive mechanism of interactions of açaí and anticancer drugs is still underway. We are also presently investigating the potential of Ashwagandha taken by older adults to produce pharmacokinetic interactions through CYP inhibition and induction. The results of these studies will provide evidence for the safe use of açaí and ashwagandha botanical dietary supplements.

Selected Publications

Contribute to my Google Scholar i10-Index of 38 and Google Scholar H-index of 21.

• Zhang, Y, Rants'o, TA, Jung, D, Lopez, E, Abbott, K, Pondugula, SR, McLendon, L, Qian, J, Hansen, RA, Calderón, AI. Screening for CYP3A4 inhibition and induction coupled to parallel artificial membrane permeability assay (PAMPA) for prediction of botanical-drug interactions: The case of açaí and maca. Phytomedicine (2019): 152915. PMID: 30981185
• Fahim, SM, Mishuk, AU, Cheng, N, Hansen, R, Calderón, AI, Qian, J. Adverse event reporting patterns of concomitant botanical dietary supplements with CYP3A4 interactive & CYP3A4 non-interactive anticancer drugs in the U.S. Food and Drug Administration Adverse Event Reporting System (FAERS). Expert Opin Drug Saf. 2019. PMID: 30576263
• Simithy, J, Fuanta, NR, Hobrath, JV, Alturki, MA, Wahba, AE, Rath, J, Hamann, MT, DeRuiter, J, Goodwin, DC, Calderón, AI. Slow, tight-binding inhibition of Mycobacterium tuberculosis shikimate kinase by manzamine alkaloids. Biochemistry 2018; 57(32):4923-4933. PMID: 30063132
• Simithy, J, Fuanta, NR, Hobrath, JV, Kochanowska-Karamyan, A, Hamann, MT, Goodwin, DC, Calderón, AI. Mechanism of irreversible inhibition of Mycobacterium tuberculosis shikimate kinase by ilimaquinone. Biochimica et Biophysica Acta – Proteins and Proteomics 2018;1866(5-6):731-739. PMID: 29654976
• Alturki, MS, Fuanta, NR, Jarrard, MA, Hobrath, JV, Goodwin, DC, Rants'o, TA, Calderón, AI. A multifaceted approach to identify non-specific enzyme inhibition: Application to Mycobacterium tuberculosis shikimate kinase.  Bioorg Med Chem Lett. 2018. 28(4):802-808. PMID: 29366649.
• Li, C, Hansen, RA, Chou, C, Calderón, AI, Qian, J.  Trends in botanical dietary supplement use among US adults by cancer status: The National Health and Nutrition Examination Survey, 1999 to 2014.  Cancer. 2018. 124(6):1207-1215. PMID: 29211315
• Pisarčíková, J, Oceľová, V, Faix, Š, Plachá, I, Calderón, AI. Identification and quantification of thymol metabolites in plasma, liver, and duodenal wall of broiler chickens using UHPLC-ESI-QTOF-MS.  Biomedical Chromatography 2017. 31(5). PMID: 27808421
• Almalki, AJ, Zaher, A, Simithy, J, Keller, WJ, Tripp, M, Calderón, AI. LC-MS based Quality Assessment of a Traditional Chinese Medicine YANG XIN Formulation.  Planta Medica, 2016; 82(13):1208-16. PMID: 27124240
• Burkard, L, Scheuermann, A, Simithy, J, Calderón, AI.  Development of a functional assay to detect inhibitors of Plasmodium falciparum glutathione reductase utilizing liquid chromatography-mass spectrometry.  Biomed Chromatogr. 2016; 30(4):543-547. PMID: 26257195
• Simithy, J, Gill, G, Wang, Y, Goodwin, DC, Calderón, AI.  Development of an ESI-LC-MS-based assay for kinetic evaluation of Mycobacterium tuberculosis shikimate kinase activity and inhibition.  Analytical Chemistry 2015; 87(4):2129-36. PMID: 25629762
• Zaher, AM, Makboul, MA, Moharram, AM, Tekwani, BL, Calderón, AI.  A new enniatin antibiotic from the endophyte Fusarium tricinctum Corda. Journal of Antibiotics 2015; 68(3):197-200. PMID: 25315756
• Zaher, AM, Makboul, MA, Moharram, AM, Calderón, AI.  LC-MS metabolite fingerprinting and MtSK-based screening of an endophyte Bartalinia pondoensis Marinc of Citrus aurantum L. Journal of Chromatography B. 2014; 970:18-23. PMID: 25222744
• Sterling, C, Crouch, R, Russell, DJ, Calderón, AI.  1H NMR quantification of major saccharides in açaí raw materials: a comparison of the internal standard methodology with the absolute intensity qNMR method.  Phytochemical Analysis. 2014; 24(6):631-637. PMID: 23703884
• Munigunti, R, Calderón, AI. Development of liquid chromatography/mass spectrometry based screening assay for PfTrxR inhibitors using relative quantitation of intact thioredoxin.  Rapid Communications in Mass Spectrometry 2012; 26:2051-2056. PMID: 22847705
• Mulabagal, V, Keller, WJ, Calderón, AI.  Quantitative analysis of anthocyanins in Euterpe oleracea (açaí) dietary supplement raw materials and capsules by Q-TOF LC/MS.  Pharmaceutical Biology 2012; 50:1289-1296. PMID: 22900515
• Mulabagal, V, Calderón, AI. Liquid chromatography/mass spectrometry based fingerprinting analysis and mass profiling of Euterpe oleracea (açaí) dietary supplement raw materials.  Food Chemistry 2012; 134:1156-1164. PMID: 23107743
• Munigunti, R,  Nelson, N, Mulabagal, V, Gupta, MP, Brun, R, Calderón, AI.  Identification of oleamide in Guatteria recurvisepala by LC/MS based Plasmodium falciparum thioredoxin reductase ligand binding method. Planta Medica 2011; 77: 1749-1753.  PMID: 21567357
• Munigunti, R, Mulabagal, V, Calderón, AI.  Screening of natural compounds for ligands to PfTrxR by ultrafiltration and LC-MS based binding assay.  Journal of Pharmaceutical and Biomedical Analysis 2011; 55:265-271. PMID: 21353756
• Mulabagal, V, Calderón, AI.  Development of an ultrafiltration-liquid chromatography/mass spectrometry (UF-LC/MS) based ligand-binding assay and an LC/MS based functional assay for Mycobacterium tuberculosis shikimate kinase.  Analytical Chemistry 2010; 82:3616-321. PMID: 20394394
• Mulabagal, V, Calderón, AI.  Development of binding assays to screen ligands for Plasmodium falciparum thioredoxin and glutathione reductases by ultrafiltration and liquid chromatography/mass spectrometry.  Journal of Chromatography B 2010; 878:987-993. PMID: 20335080