Drug Discovery from Natural Products

This project goes back two decades. It started before 2000 as a cooperative group that included ecologists, botanists, chemists and biologists from the Smithsonian Tropical Research Institute, University of Panama and INDICASAT AIP, along several universities in the United States. The project, initiated by Philys Coley and Tom Kursar from STRI, was funded by the NIH, the NSF and the USDA with some private partners like Dow Agrochemicals or the Japanese pharmaceutical EISAI. 


The program was so successful that it was renewed three times for a total of 15 years of continued run. Later, the UN Global Emergency Fund funded three more years of the collaboration and then it has also received funding from the national Secretariat of Science, Technology and Innovation of Panama.


The project works mainly with the collaboration of researchers at INDICASAT AIP who try to add value to our biodiversity through the discovery of bioactivity in crude extracts, infusions, fractions or purified compounds from the rich biodiversity of Panama.

Because of this mission, the program has received funding from the Endowment for Water, Wild Life and Protected Areas to establish a Biobank of microorganisms with the data set of bioactivities and taxonomic classification, among other parameters.


Structure Modification, Antidiatom, Antiplasmodial and Toxic Evaluations of a Series of New Marine-Derived 14-Membered Resorcylic Acid Lactone Derivatives. Wei-Feng Xu, Na-Na Wu, Yan-Wei Wu, Yue-Xuan Qi, Mei-Yan Wei, Laura M. Pineda, Michelle Ng, Carmenza Spadafora, Ji-Yong Zheng, Ling Lu, Chang-Yun Wang, Yu-Cheng Gu, Chang-Lun Shao. Marine Life Science & Technology (2021), 1-10. 10.1007/s42995-021-00103-0 


 Bufadienolides from the skin secretions of the Neotropical toad Rhinella alata (Anura: Bufonidae): antiprotozoal activity against Trypanosoma cruzi. Candelario Rodriguez, Roberto Ibáñez, Luis Mojica, Michelle NG, Carmenza Spadafora, Armando A. Durant-Archibold, Marcelino Gutiérrez. (2021) Molecules, 26 (14), 4217. https://doi.org/10.3390/molecules26144217    


Semisynthesis, antiplasmodial activity, and mechanism of action studies of isocoumarin derivatives. Lorena Coronado, Xue-Qing Zhang, Doriana Dorta, Nerea Escala, Laura Pineda, Michelle Ng, Esther Del Olmo, Chang-Yun Wang, Yu-Cheng Gu, Chang-Lun Shao, Carmenza Spadafora. Journal of Natural Products May 21, (2021) 84, 5, 1434–1441. https://doi.org/10.1021/acs.jnatprod.0c01032  


19-hydroxy-bufalin, a major bufadienolide isolated from the parotoid gland secretions of the Panamanian endemic toad Rhinella centralis (Bufonidae), inhibits the growth of Trypanosoma cruzi. Candelario Rodriguez, Armando Durant, Roberto Ibañez, Michelle Ng, Carmenza Spadafora, Marcelino Gutierrez. Toxicon 177 (2020) 89–92. doi: 10.1016/j.toxicon.2020.02.009 


  Antiplasmodial activity from leaves of Cocos nucifera in Plasmodium berghei infected mice. Nicole M. Tayler, Rosa De Jesús de Durán, Rita Spadafora, Lorena M. Coronado, Carmenza Spadafora. J Parasit Dis 44, 305–313 (2020). https://doi.org/10.1007/s12639-020-01207-7 


Access and Benefit Sharing under the Nagoya Protocol – Quo vadis? Six Latin American case studies assessing opportunities and risk. Michael Heinrich, Francesca Scotti, Adolfo Andrade-Cetto, Monica Berger-Gonzalez, Javier Echeverría, Fabio Friso, Felipe Garcia-Cardona, Alan Hesketh, Martin Hitziger, Caroline Maake, Matteo Politi, Carmenza Spadafora and Rita Spadafora. Frontiers in Pharmacology 11, 765, 2020. https://doi.org/10.3389/fphar.2020.0076 

Analysis of the antiparasitic and anticancer activity of the Coconut Palm (Cocos nucifera L. ARECACEAE) from the Natural Reserve of Punta Patiño, Darién. Nicole Tayler Sucre, Cristopher A. Boya, Liuris Herrera, Jamie Moy, Michelle Ng, Laura Pineda, Alejandro Almanza, Sara Rosero, Lorena Coronado, Ricardo Correa, Ricardo Santamaría, Zuleima Caballero, Armando A. Durant-Archibold, Kevin J. Tidgewell, Marcy J. Balunas, William H. Gerwick, Alida Spadafora, Marcelino Gutiérrez, Carmenza Spadafora. PLOS ONE 2019 Apr 2;14(4):e0214193

Antiparasitic Compounds from the Panamanian Marine Bacterium Pseudomonas aeruginosa. Sergio Martínez-Luis, Lilia Cherigo, Carmenza Spadafora and Marcelino Gutiérrez. Natural Product Communication 14 (1), 31-32. 2019.

Pumilacidins from the Octocoral-Associated Bacillus sp. DT001 Display Anti-Proliferative Effects in Plasmodium falciparum. Torres-Mendoza D, Coronado LM, Pineda LM, Guzmán HM, Dorrestein PC, Spadafora C, Gutiérrez M. Molecules. 2018 Aug 29;23(9).

Bastimolide B, An Antimalarial 24-Membered Marine Macrolide Possessing a tert-Butyl Group. Chang-Lun Shao; Xiao-Feng Mou; Fei Cao; Carmenza Spadafora; Evgenia Glukhov; Lena Gerwick; Chang-Yun Wang; William Gerwick. J Nat Prod. 2018 81(1):211-215.

Evaluation of antiparasitic, anticancer, antimicrobial and hypoglycemic properties of organic extracts from Panamanian Mangrove Plants.  Dioxelis Lopez, Carmenza Spadafora, Lilia Cherigo, Alejandro de Sedas, Sergio Martinez. Asian Pacific Journal of Tropical Medicine. 2018, 11(1):32.

Discovery, Semisynthesis, Antiparasitic and Cytotoxic Evaluation of 14-Membered Resorcylic Acid Lactones and Their Derivatives. Xue-Qing Zhang, Carmenza Spadafora, Laura M. Pineda, Michelle Ng W., Ji-Hong Sun, Wei Wang, Changyun Wang, Yucheng Gu. Scientific Reports 2017 Sep 18;7(1):11822

Discovery and Synthesis of Caracolamide A, an Ion Channel Modulating Dichlorovinylidene Containing Phenethylamide from a Panamanian Marine Cyanobacterium cf. Symploca Species. Naman CB, Almaliti J, Armstrong L, Caro-Díaz EJ, Pierce ML, Glukhov E, Fenner A, Spadafora C, Debonsi HM, Dorrestein PC, Murray TF, Gerwick WH. J Nat Prod. 2017, 80(8):2328-2334.

Imaging mass spectrometry and MS/MS molecular networking reveals chemical interactions among cuticular bacteria and pathogenic fungi associated with fungus-growing ants. Cristopher A. Boya P, Hermógenes Fernández-Marín, Luis C. Mejía, Carmenza Spadafora, Pieter C. Dorrestein and Marcelino Gutiérrez. Scientific Reports. 2017 Jul 17;7(1):5604

Dudalawamides A-D, Antiparasitic clyclic depsipeptides from the marine cyanobacterium Moorea producens. J Almaliti, KL Malloy, E Glukhov, C Spadafora, M Gutiérrez, WH Gerwick. Journal of Natural Products. 2017 Jun 23;80(6):1827-1836

Marine cyanobacteria-derived serotonin receptor 2C active fraction induces psychoactive behavioral effects in mice. Neil C. Lax, Kh Tanvir Ahmed, Christopher M. Ignatz, Carmenza Spadafora, Benedict J. Kolber, and Kevin Tidgewell. Pharm Biol. 2016 May 14:1-9

Medusamida A, a Panamanian Cyanobacterial Depsipeptide with Multiple β-Amino Acids. Fenner AM, Engene N, Spadafora C, Gerwick WH, Balunas MJ. Org Lett. 2016 Feb 5;18(3):352-5. doi: 10.1021/acs.orglett.5b03110

Phytochemical composition, antiparasitic and α-glucosidase inhibition activities from Pelliciera rhizophorae. López D, Cherigo L, Spadafora C, Loza-Mejía MA, Martínez-Luis S. Chem Cent J. 2015 Sep 28;9(1):53

Bastimolide A, a Potent Antimalarial Polyhydroxy Macrolide from the Marine Cyanobacterium Okeania hirsuta. Shao CL, Linington RG, Balunas MJ, Centeno A, Boudreau P, Zhang C, Engene N, Spadafora C, Mutka TS, Kyle DE, Gerwick L, Wang CY, Gerwick WH. J Org Chem. 2015 Aug 21;80(16):7849-55

Chemical and bioactive natural products from Microthyriaceae sp., an endophytic fungus from a tropical grass. Celso Almeida, Humberto Ortega, Sarah Higginbotham, Carmenza Spadafora, A. Elizabeth Arnold, Phyllis D. Coley, Kursar Thomas A, William H. Gerwick and Luis Cubilla-Rios. Letters of Applied Microbiology 10 MAR 2014 03:29AM EST | DOI: 10.1111/lam.12245

Sloth fur as a novel source of fungi with potent anti-parasitic, anti-cancer and anti-bacterial bioactivity Sarah Higginbotham, Weng Ruh Wong, Roger G. Linington, Carmenza Spadafora, Liliana Iturrado, A. Elizabeth Arnold. PLoS One 2014 Jan 15;9(1):e84549. doi: 10.1371/journal.pone.0084549

Antimalarial activity and metabolic profiling by HS-SPME-GC-MS of Plinia cerrocampanensis leaf essential oil.  Armando A Durant, Candelario Rodriguez, Liuris Herrera, Alejandro Almanza, Ana I Santana, Carmenza Spadafora and Mahabir P Gupta. Malaria J 01/2014; 13(1):18  doi:10.1186/1475-2875-13-18

Bioactivity of fungal endophytes as a function of endophyte taxonomy and the taxonomy and distribution of their host plants. Higginbotham SJ, Arnold AE, Ibañez A, Spadafora C, Coley PD, Kursar, TA (2013). PLoS ONE 8(9): e73192. doi:10.1371/journal.pone.0073192

Antitrypanosomal Alkaloids from the marine bacterium Bacillus pumilu. Sergio Martínez-Luis, José Félix Gómez, Carmenza Spadafora, Héctor M. Guzmán, Marcelino Gutiérrez, Molecules, 2012 Sep 18;17(9):11146-55.

Coibacins A-D, Antileishmanial Marine Cyanobacterial Polyketides with Intriguing Biosynthetic Origins. Balunas MJ, Grosso MF, Villa FA, Engene N, McPhail KL, Tidgewell K, Pineda LM, Gerwick L, Spadafora C, Kyle DE, Gerwick WH. Org Lett. 2012 Aug 3;14(15):3878-3881

Coibanoles, a new class of meroterpenoids produced by Pycnoporus sanguineus. Eunice Molinar, Nivia Rios, Carmenza Spadafora, A. Elizabeth Arnold, Phyllis D. Coley, Thomas A. Kursar, William H. Gerwick, Luis Cubilla-Rios  Tetrahedron Letters  Volume 53, Issue 8, 22 February 2012, Pages 919–922

Antiparasitic and anticancer constituents of the endophytic fungus Aspergillus sp. strain F1544.  Martínez-Luis S, Cherigo L, Arnold E, Spadafora C, Gerwick WH, Cubilla-Rios L.  Natural product communications. 02/2012; 7(2):165-8.

Evaluation of phytotoxic, cytotoxic and antiparasitic in vitro activities of Borreria verticillata, a weed of Panamanian coffee crops. L Cherigo, J Lezcano, C Spadafora, Sergio Martínez-Luis. Bioscience Research, 2012 9(2):82-86

Credneramides A and B: Neuromodulatory Phenethylamine and Isopentylamine Derivatives of a Vinyl Chloride-Containing Fatty Acid from cf. Trichodesmium sp. nov. Malloy KL, Suyama TL, Engene N, Debonsi H, Cao Z, Matainaho T, Spadafora C, Murray TF, Gerwick WH. J Nat Prod. 2012 Jan 27;75(1):60-6

Screening and evaluation of antiparasitic and in vitro anticancer activities of Panamanian endophytic fungi. Martínez-Luis S, Cherigo L, Higginbotham S, Arnold E, Spadafora C, Ibañez A, Gerwick WH, Cubilla-Rios L. Int Microbiol. 2011 Jun;14(2):95-102.

Chemical constituents from the new endophytic fungus Mycosphaerella sp. nov. and their anti-parasitic activity. Moreno, E., Varughese, T., Spadafora, C., Arnold, AE,  Coley, PD, Kursar, TA, Gerwick, WH and  Cubilla-Rios, L. Natural Product Communications, (2011) Vol. 6(6):835-840

Cytotoxic Veraguamides, Alkynyl Bromide-containing cyclic Depsipeptides from the marine Cyanobacterium cf. Osciallatoria margaritiferaEmily Mevers,Wei-Ting Liu, Niclas Engene, Hosein Mohimani, Tara Byrum, Pavel A. Pevzner, Pieter C. Dorrestein, Carmenza Spadafora, and William H. Gerwick. (2011) J Nat Prod. (2011) 74(5):928-36.

In vitro and in vivo experimental models in drug screening and development for Chagas disease.  Romanha AJ, Castro SL, Soeiro Mde N, Lannes-Vieira J, Ribeiro I, Talvani A, Bourdin B, Blum B, Olivieri B, Zani C, Spadafora C,, Chiari E, Chatelain E, Chaves G, Calzada JE, Bustamante JM, Freitas-Junior LH, Romero LI, Bahia MT, Lotrowska M, Soares M, Andrade SG, Armstrong T, Degrave W, Andrade Zde A.. Memórias do Instituto Oswaldo Cruz  (2010) 105(2): 233-238.

Additional anti-leishmanial constituents of the Panamanian Endophytic fungus Edenia sp.  Martínez-Luis S; Cherigo, L; Spadafora, C;, Gerwick, WH.; and Cubillas-Rios, L   Rev. Latinoamer. Quím. (2009)   37, (2), 104-114.

The program has partnered with NGO ANCON to add value to the products of their private natural reserve in Punta Patiño, Darién. Private companies like INDIGENA BIODIVERSITY or Oxford Biotrans from the UK are working with our group at INDICASAT AIP in search of leads with commercial posibilities.