Manfred G. Reinecke(m.reinecke@tcu.edu)
Professor Emeritus and Cecil and Ida Green Distinguished Emeritus Tutor

Organic and Natural Products Chemistry

 
Research Interests

Professor Reinecke’Äôs research interests involve all aspects of the chemistry of natural products including their isolation, structure determination, synthesis and biological activity. Working in collaboration with anthropologists, botanists, pharmacologists, and microbiologists his group examines characterized medicinal plants from Pakistan, Bolivia and China as sources of lead compounds for drug development. Isolation of these active compounds involves preparative and analytical chromatography and is directed by bioassays for anti-cancer, anti-HIV, anti-bacterial, anti-fungal, anti-trypanosomal, insecticidal and CNS activity. Structure determination relies heavily on NMR, mass spectral, UV and IR methods. Syntheses are undertaken to supply additional active compounds for biological evaluation, to determine structure-activity correlations and, with appropriate isotopic labeling, to study biochemical mechanisms of action. Several lead compounds with anti-cancer, anti-TB and, especially, anti-HIV activity have recently been found and studied.

Recent efforts have centered on studies of compounds with anti-HIV activity originally detected in several medicinal plants used by the Kallawaya Indians of Bolivia [5,6]. Four different active compounds isolated from four different plants all turned out to be dicaffeoyl derivatives of quinic acid [DCQA's]. Significantly their anti-HIV activity was shown [3,4] to be due to the inhibition of integrase, the only one of three known viral enzymes [the others being reverse transcriptase and protease] for which no drugs were known. Chicoric acid [dicaffeoyltartaric acid], a simple analogue of DCQA, was synthesized, also shown to be a selective inhibitor of HIV-1 Integrase [2] and therefore was chosen as the lead compound for an on-going synthetic study of the structure-activity relationships responsible for anti-HIV activity by inhibition of HIV-integrase [1].

 

(HIV structure, courtesy of J. Chem. Ed. Used with permission.)
Bibliography

[1] Structure-Activity Relationships: Analogues of the Dicaffeoyl-quinic and Dicaffeoyltartaric acids as Potent Inhibitors of Human Immunodeficiency Virus Type 1 (HIV-1) Integrase and Replication, Peter J. King, Guo-Xiang Ma, Wenfang Miao, Qi Jia, Brenda R. McDougall, Manfred G. Reinecke, Chris Cornell, Jean Kuan, Tracey Kim and W. Edward Robinson, Jr., J. Med. Chem., 1999, 42 [3], 497-509.

[2] Dicaffeoylquinic and Dicaffeoyltartaric Acids are Selective Inhibitors of HIV-1 Integrase, Brenda McDougall, Peter J. King, Bor Wen Wu, Zdenek Hostomsky, Manfred G. Reinecke, and W. Edward Robinson, Jr., Antimicrobial Agents and Chemotherapy, 1998, 42, 140-146.

[3] Dicaffeoylquinic Acid Inhibitors of Human Immunodeficiency Virus (HIV) Integrase: Inhibition of the Core Catalytic Domain of HIV Integrase, W. Edward Robinson, Jr. Mara Cordeiro, Samia Abdel-Malek, Qi Jia, Samson A. Chow, Manfred G. Reinecke and William M. Mitchell, Molecular Pharmacology, 1996, 50, 846-855.

[4] Inhibitors of HIV-1 Replication that Inhibit HIV Integrase, W. Edward Robinson, Jr., Manfred G. Reinecke, Samia Abdel-Malek, Qi Jia, and Samson A. Chow, Proceedings, National Academy of Sciences, 1996, 93, 6326-6331.

[5] Drug leads from the Kallawaya Herbalists of Bolivia; 1. Background, Rationale, Protocol and Anti-HIV Activity, Samia Abdel-Malek, Joseph W. Bastien, William F. Mahler, Qi Jia , Manfred G. Reinecke, W. Edward Robinson, Jr., Yong-hua Shu, and Jaime Zalles-Asin, Journal of Ethnopharmacology, 1996, 50, 157-166.

[6] Kallawaya-Bolivian Herbalists; Analysis of Their Medicinal Plants for Leads to Anti-HIV, Anti-Tumor, Anti-Chagas Drugs, Joseph W. Bastien, Samia Abdel-Malek, Jia Qi, Manfred G. Reinecke, Thomas H. Corbett, Fred A. Valeriote William F. Mahler, W. Edward Robinson, Jr., & Jaime Zalles-Asin, in Ethnobiology in Human Welfare, 1996, S.K.Jain, Ed., Deep Publications, New Dehli, pp.211-222.