Scott Gary Franzblau

My motivation for finding new drugs for tuberculosis stems from a general desire to help alleviate suffering from diseases that disproportionately affect the poor and that have been neglected by the very countries that have the resources to make a difference. The success that we had in going from the lab to the clinic in leprosy in the 90s, gave me confidence that we can do the same for TB as these diseases are caused by related bacteria. The ITR is pursuing several strategies for discovery of new anti-TB agents. This includes large scale screening of both natural and synthetic compounds for those that demonstrate specificity of activity (i.e. inhibit the TB bacillus but not mammalian cells). Lead compounds are then optimized by semi-synthesis. In addition we are attempting to optimize the anti-TB activity of classes of antibiotics used for other infections but that have not been clinically active in tuberculosis. Activity of all lead compounds are assessed in macrophage and mouse models of TB. Ultimately clinical trials will be conducted with collaborators in TB-endemic regions.

• Macabeo APG , Letada AG, Budde S, Faderl C, Dahse HM, Franzblau SG, Alejandro GJD , Pierens GK, Garson MJ. Antitubercular and Cytotoxic Chlorinated seco-Cyclohexenes from Uvaria alba.. Journal of natural products. 2017;80(12):3319-3323. doi:10.1021/acs.jnatprod.7b00679.

• Choi PJ, Sutherland HS, Tong AST , Blaser A, Franzblau SG, Cooper CB, Lotlikar MU, Upton AM, Guillemont J, Motte M, Queguiner L, Andries K, Van den Broeck W, Denny WA, Palmer BD. Synthesis and evaluation of analogues of the tuberculosis drug bedaquiline containing heterocyclic B-ring units.. Bioorganic & medicinal chemistry letters. 2017;27(23):5190-5196. doi:10.1016/j.bmcl.2017.10.042.

• Börger C, Brütting C, Julich-Gruner KK, Hesse R, Kumar VP, Kutz SK, Rönnefahrt M, Thomas C, Wan B, Franzblau SG, Knölker HJ. Anti-tuberculosis activity and structure-activity relationships of oxygenated tricyclic carbazole alkaloids and synthetic derivatives.. Bioorganic & medicinal chemistry. 2017;25(22):6167-6174. doi:10.1016/j.bmc.2016.12.038.

• Thompson AM, Bonnet M, Lee H, Franzblau SG, Wan B, Wong GS, Cooper CB, Denny WA. Antitubercular Nitroimidazoles Revisited: Synthesis and Activity of the Authentic 3-Nitro Isomer of Pretomanid.. ACS medicinal chemistry letters. 2017;8(12):1275-1280. doi:10.1021/acsmedchemlett.7b00356.

• Gao W, McAlpine JB, Choules MP, Napolitano JG, Lankin DC, Simmler C, Ho NA, Lee H, Suh JW, Burton IW, Cho S, Franzblau SG, Chen S, Pauli GF. Structural Sequencing of Oligopeptides Aided by ¹H Iterative Full-Spin Analysis.. Journal of natural products. 2017;80(10):2630-2643. doi:10.1021/acs.jnatprod.7b00207.

• Dos Santos Fernandes GF, de Souza PC, Moreno-Viguri E, Santivañez-Veliz M, Paucar R, Pérez-Silanes S, Chegaev K, Guglielmo S, Lazzarato L, Fruttero R, Man Chin C, da Silva PB, Chorilli M, Solcia MC, Ribeiro CM, Silva CSP , Marino LB, Bosquesi PL, Hunt DM, de Carvalho LPS , de Souza Costa CA, Cho S, Wang Y, Franzblau SG, Pavan FR, Dos Santos JL. Design, Synthesis, and Characterization of N-Oxide-Containing Heterocycles with in Vivo Sterilizing Antitubercular Activity.. Journal of medicinal chemistry. 2017;60(20):8647-8660. doi:10.1021/acs.jmedchem.7b01332.

• Brengel C, Thomann A, Schifrin A, Allegretta G, Kamal AAM , Haupenthal J, Schnorr I, Cho S, Franzblau SG, Empting M, Eberhard J, Hartmann RW. Biophysical Screening of a Focused Library for the Discovery of CYP121 Inhibitors as Novel Antimycobacterials.. ChemMedChem. 2017;12(19):1616-1626. doi:10.1002/cmdc.201700363.

• Liu R, Lyu X, Batt SM, Hsu MH, Harbut MB, Vilchèze C, Cheng B, Ajayi K, Yang B, Yang Y, Guo H, Lin C, Gan F, Wang C, Franzblau SG, Jacobs WR, Jr GS, Besra EF, Johnson M, Petrassi AK, Chatterjee K, Fütterer F, Wang . Determinants of the Inhibition of DprE1 and CYP2C9 by Antitubercular Thiophenes.. Angewandte Chemie (International ed. in English). 2017;56(42):13011-13015. doi:10.1002/anie.201707324.

• Tong AST , Choi PJ, Blaser A, Sutherland HS, Tsang SKY , Guillemont J, Motte M, Cooper CB, Andries K, Van den Broeck W, Franzblau SG, Upton AM, Denny WA, Palmer BD, Conole D. 6-Cyano Analogues of Bedaquiline as Less Lipophilic and Potentially Safer Diarylquinolines for Tuberculosis.. ACS medicinal chemistry letters. 2017;8(10):1019-1024. doi:10.1021/acsmedchemlett.7b00196.

• Warit S, Rukseree K, Prammananan T, Hongmanee P, Billamas P, Jaitrong S, Chaiprasert A, Jaki BU, Pauli GF, Franzblau SG, Palittapongarnpim P. In Vitro Activities of Enantiopure and Racemic 1′-Acetoxychavicol Acetate against Clinical Isolates of Mycobacterium tuberculosis.. Scientia pharmaceutica. 2017;85(3). doi:10.3390/scipharm85030032.