Alice M. Clark
Vice Chancellor for Research and Sponsored Programs
Frederick A.P. Barnard Distinguished Professor
Research Professor in the Research Institute of Pharmaceutical Sciences
Professor of Pharmacognosy
Dr. Clark received her B.S. degree in Microbiology from Troy State University, graduating magna cum laude in 1973. She holds the M.S. in Pharmacognosy and received the Ph.D. in Pharmacognosy in 1978 from The University of Mississippi, where she was an American Foundation for Pharmaceutical Education Fellow. She joined the Drug Dynamics Institute and the College of Pharmacy of the University of Texas at Austin in 1978 as a Robert F. Welch Research Fellow. Dr. Clark was appointed Research Assistant Professor of Pharmacognosy at The University of Mississippi in 1980, Assistant Professor in 1983, Associate Professor and Research Associate Professor of RIPS in 1985, and achieved her current rank of Professor of Pharmacognosy and Research Professor of RIPS in 1990. In 1993, she was appointed as F.A.P. Barnard Distinguished Professor. In 1995, she was appointed as Interim Director of the National Center for the Development of Natural Products, and in 1996, Director of the National Center for Natural Products Research. In 1998, she became Associate Editor for the Journal of Natural Products. In 2001, she was appointed Vice Chancellor for Research and Sponsored Programs at The University of Mississippi.
Click here to see Research in Progress and Publications
Research in Progress
The Department of Pharmacognosy has developed a nationally recognized antibiotic discovery program over the last 10 years, most recently focusing on the discovery and development of prototype antibiotics with potential clinical utility for the treatment of opportunistic infections in immunocompromised hosts. These infections rarely occur in patients with normally functioning immune systems, but are common and often fatal in AIDS patients and in other patients with any type of immunosuppression (i.e., cancer patients and organ transplant recipients).
There is an urgent need for the discovery and development of totally new, prototype antibiotics, which may serve as "leads" for the development of new classes of chemotherapeutic agents that do not share the same toxicities and cross-resistance of the existing agents. Natural products have, in the past, provided such prototypes. It is reasonable to assume that if new prototype antibiotics are to be found that have different structures with different or supplemental activities from the ones in current use, then a source other than the more traditional microorganisms must be investigated. In particular, higher plants are an excellent choice, chiefly because of their seemingly infinite variety of novel organic molecules.
Dr. Clark's current research program, aimed at addressing the inadequacy of chemotherapy of opportunistic infections in immunocompromised hosts, is unique in that it is a major drug development program within an academic institution that combines drug discovery, in vitro and in vivo evaluations. An important characteristic of this program is that it addresses all aspects of drug discovery and development up to a preliminary assessment of potential clinical utility, including investigations into the mechanism(s) of action of novel antibiotics and the development of novel, but simple in vitro bioassay systems for use in the discovery of antibiotics acting at unique and specific microbial molecular targets. Utilization of mechanism of action information and mechanism-based assay systems should facilitate the discovery and development of highly selective antibiotics with potential use in the treatment of opportunistic infections.
Dr. Clark's interests also include the utilization of microorganisms a predictive models for drug metabolism and as synthetic adjuncts. It is well known that microorganisms can carry out regiospecific and stereospecific transformations of complex molecules in a mild and often high yielding manner. Thus, microbial systems are sought to effect specific changes in the structure of biologically active substances that may not be amenable to chemical transformations. Examples of projects in this area include the microbial modification of several biologically active sesquiterpenes.
(* denotes corresponding author)
A.M. Clark, E.S. Watson, M.K. Ashfaq, and C.D. Hufford, "In Vivo Efficacy of Antifungal Oxoaporphine Alkaloids in Experimental Disseminated Candidiasis", Pharm. Res. 4, 495 (1987).
C.D. Hufford, S.-C. Liu, and A.M. Clark, "Antifungal Activity of Trillium grandiflorum Constituents", J. Nat. Prod. 54, 94 (1988).
T.M. Jurgens and A.M. Clark, "The Metabolism of CGP-291: The Use of Microorganisms as Models of Mammalian Metabolism", Pharm. Res. 7, 742 (1990).
S.-C. Liu, B. Oguntimein, C.D. Hufford, and A.M. Clark, "3-Methoxysampangine, A Novel Antifungal Copyrine Alkaloid from Cleistopholis patens", Antimicrob. Ag. Chemother. 34, 529 (1990).
A.M. Clark and C.D. Hufford, "Antifungal Alkaloids", The Alkaloids (Ed. G.A. Cordell), Academic Press, (Invited chapter) pp. 117-150 (1992).
J.K. Zjawiony, A.R. Srivastava, C.D. Hufford, and A.M. Clark, "Chemistry of Sampangines", Heterocycles, 39(2) 779-800 (1994).
A.L. Okunade, S. Liu, A.M. Clark, C.D. Hufford, and R.D. Rogers, "Sesquiterpene Lactones from Peucephyllum shottii," Phytochemistry, 35 (1) 191-194 (1994).
E. Li, A.M. Clark and C.D. Hufford, "Antifungal Evaluation of Pseudolaric acid B, A Major Constituent of Pseudolarix Kaempferi", J. Nat. Prod., 58 (1) 57-67, 1995.
E. Li, A.M. Clark and C.D. Hufford, "Antifungal Evaluation of Pseudolaric acid B, A Major Constituent of Pseudolarix Kaempferi", J. Nat. Prod., 58 (1) 57-67 (1995).
I.A. Khan, A.M. Clark and J.D. McChesney, "Antifungal Activity of a New Triterpenoid Glycoside from Pithecellobium racemosum (M.)," Pharmaceutical Research, 14 (3) 358-361 (1997).
A.M. Clark, "Natural Products as a Resource for New Drugs," Pharmaceutical Research, 13 (8) 1133-1141 (1997).
J.K. Zjawiony, A.A. Khalil, A.M. Clark, C.D. Hufford and J.K. Buolamwini, "Studies on Methoxylation in the 7H-Naphtho[1,2,3-i,j][2,7] naph-thyridin-7-one System," J. Heterocyclic Chem., 34, 1233-1237 (1997).
X. Li, H.N. ElSohly, A.C. Nimrod and A.M. Clark, "Antifungal jujubogenin saponins from Colubrina retusa," Journal of Natural Products, 62 (5), 674-677 (1999).
S.Y. Ablordeppey, P. Fan, A.M. Clark and A. Nimrod, “Probing the N-5 Region of the Indoloquinoline Alkaloid, Cryptolepine for Anticryptococcal Activity,” Biorganic & Medicinal Chemistry, 7, 343 (1999).
L.G. Mardenborough, P.C. Fan, S.Y. Ablordeppey, A. Nimrod and A.M. Clark, “Identification of a Novel Antifungal Agent Based on a Pharmacophoric Group In Cryptolepine,” Medicinal Chemistry Research, 9:2, 118-132 (1999).
X.-C. Li, H.N.ElSohly, A.C. Nimrod and A.M. Clark, “Two Auronols from Pseudolarix amabilis,” Journal of Natural Products, 62 (5) 767-769 (1999).
K.Y. Orabi, E. Li, A.M. Clark and C.D. Hufford, “Microbial Transformation of Sampangine,” Journal of Natural Products, 62 (7) 988-992 (1999).
A.L. Okunade, A.M. Clark, C.D. Hufford and B.O. Oguntimein, “Azaanthraquinone: An Antimicrobial Alkaloid from Mitracarpus scaber,” Planta Medica, 65, 447-448 (1999).
H.N. ElSohly, S. Danner, X.-C. Li, A.C. Nimrod and A.M. Clark, “New Antimycobacterial Saponin from Colubrina retusa,” Journal of Natural Products, 62 (9) 1341-1342 (1999).
X-C. Li, H.N. ElSohly, C.D. Hufford, and A.M. Clark, “NMR assignments of ellagic acid derivatives,” Magnetic Resonance in Chemistry, 37, 856-859 (1999).
X-C. Li, H.N. ElSohly, A.C. Nimrod, and A.M. Clark, “Antifungal Activity of (-)-Epigallocatechin Gallate from Coccoloba dugandiana,” Planta Medica, 65, 780 (1999).
K.Y. Orabi, A.M. Clark, and C.D. Hufford, “Microbial Transformation of Benzosampangine,” Journal of Natural Products, 63 (3) 396-398 (2000).
X.-C. Li, H.N. ElSohly, and A.M. Clark, “7-Caffeoylsedoheptulose from Nyssa sylvatica,” Phytochemistry, 53, 1033-1037 (2000).
K.Y. Orabi, L.A. Walker, A.M. Clark, and C.D. Hufford, “Characterization of the Major Metabolite of Sampangine in Rats,” Journal of Natural Products, 63, 685-687 (2000).
M. Ilias, K.A. El Sayed, J.S. Mossa, M.S. Al-Said, F.S. El-Feraly, A.M. Clark, C.D. Hufford, S. Oh, and A.M.S. Mayer, “Bioactive 12-Oleanene Triterpene and Secotriterpene Acids from Maytenus undata,” Journal of Natural Products, 63 (5) 605-610 (2000).
Z. Zhang, H.N. ElSohly, M.R. Jacob, D.S. Pasco, L.A. Walker, and A.M. Clark, “New Indole Alkaloids from the Bark of Nauclea orientalis,” Journal of Natural Products, 64 (8) 1001-1005 (2001).
X.-C. Li, M.R. Jacob, D.S. Pasco, H.N. ElSohly, A.C. Nimrod, L.A. Walker and A.M. Clark, “Phenolic Compounds from Miconia myriantha Inhibiting Candida Aspartic Proteases,” Journal of Natural Products, 64 (10) 1282-1285 (2001).
X.-C. Li, D.C. Dunbar, H.N. ElSohly, M.R. Jacob, A.C. Nimrod, L.A. Walker and A.M. Clark, “A New Naphthopyrone Derivative from Cassia quinquangulata and Structural Revision of Quinquangulin and Its Glycosides,” Journal of Natural Products, 64 (9) 1153-1156 (2001).
X.-C. Li, D.C. Dunbar, H.N. ElSohly, L.A. Walker and A.M. Clark, “Indolopyridoquinazoline alkaloid from Leptothyrsa sprucei,” Phytochemistry, 58, 627-629 (2001).
Z. Zhang, H.N. ElSohly, M.R. Jacob, D.S. Pasco, L.A. Walker, and A.M. Clark, "Natural Products Inhibiting Candida albicans Secreted Aspartic Proteases from Tovomita krukovii," Planta Medica, 68 (1) 49-54 (2002).
S.Y. Ablordeppey, P. Fan, S. Li, A.M. Clark, and C.D. Hufford, “Substituted Indoloquinolines as New Antifungal Agents,” Bioorganic & Medicinal Chemistry, 10, 1337-1346 (2002).
S.I. Khan, A.C. Nimrod, M. Mehrpooya, J.L. Nitiss, L.A. Walker, and A.M. Clark, “Antifungal Activity of Eupolauridine and Its Action on DNA Topoisomerases,” Antimicrobial Agents and Chemotherapy, 46 (6) 1785-1792 (2002).
Z Zhang, H.N. ElSohly, M.R. Jacob, D.S. Pasco, L.A. Walker, and A.M. Clark, “New Sesquiterpenoids from the Root of Guatteria multivenia,” Journal of Natural Products, 65 (6) 856-859 (2002).
Z. Zhang, H.N. ElSohly, M.R. Jacob, D.S. Pasco, L.A. Walker, and A.M. Clark, “Natural Products Inhibiting Candida albicans Secreted Aspartic Proteases from Lycopodium cernuum,” Journal of Natural Products, 65 (7) 979-985 (2002).
Muhammad, S. Takamatsu, J.S. Mossa, F.S. El-Feraly, L.A. Walker, and A.M. Clark, “Cytotoxic Sesquiterpene Lactones from Centaurothamnus maximus and Vicoa pentanema,” Phytotherapy Research, 17, 168-173 (2003).
A.M. Clark and L.A. Walker, "Discovery of Antifungal Agents from Natural Sources: Virulence Factor Targets," in Biologically Active Natural Products: Pharmaceuticals, S.J. Cutler and H.G. Cutler, eds., CRC Press, Ch. 7, pp. 95-107 (1999).
A.M. Clark, “Natural Products as New Drugs”, in Foye’s Principles of Medicinal Chemistry, 5th ed., W.O. Foye, T.M. Lemke, and D.A. Williams, editors, 1999.
E.A. Abourashed, A.M. Clark and C.D. Hufford, “Microbial Models of Mammalian Metabolism of Xenobiotics: An Updated Review,” Current Medicinal Chemistry, 6, 359-374 (1999).
A.M. Clark, “Higher Plant-Derived Antimicrobials”, in preparation for Society of Industrial Microbiology.
M. Slattery, M. Flagg, and A.M. Clark, “Chemotaxonomy: Research Perspective and Prospects”, in preparation for J. Nat. Prod.
C.D. Hufford and A.M. Clark, “Natural and Synthetic Substances Related to Human Health”, Pure and Applied Chemistry, 74, 10, 1957-1985 (2002).
A.M. Clark, “The Search for Mechanistically and Structurally Novel Natural Products”, in preparation for Pesticide Chemistry.
A.M. Clark, “Ethnomedicine in Drug Discovery”, Introductory chapter for proceedings of the conference, “Ethnomedicine in Drug Discovery”, in preparation.