A broad study of two new promising antimycobacterial drugs: Ag(I) and Au(I) complexes with 2-(2-thienyl)benzothiazole Guilherme Alves Pereira a , Antonio Carlos Massabni b , Eduardo Ernesto Castellano c , Luiz Antônio Sodré Costa d , Clarice Queico Fugimura Leite e , Fernando Rogério Pavan e , Alexandre Cuin a,⇑ a LQBin, Laboratório de Química BioInorgânica, Departamento de Química, Instituto de Ciências Exatas, UFJF, 36036-330 Juiz de Fora, MG, Brazil b Departamento de Química Geral e Inorgânica, Instituto de Química, UNESP, 14801-970 Araraquara, SP, Brazil c Instituto de Física, USP, 13560-000 São Carlos, SP, Brazil d NEQC, Núcleo de Estudos em Química Computacional, Departamento de Química, Instituto de Ciências Exatas, UFJF, 36036-330 Juiz de Fora, MG, Brazil e Departamento Ciências Biológicas, Faculdade de Ciências Farmacêuticas, UNESP, 14800-900 Araraquara, SP, Brazil article info Article history: Received 26 January 2012 Accepted 9 March 2012 Available online 21 March 2012 Keywords: Benzothiazole Silver Gold Tuberculosis Mycobacterium abstract Synthesis, characterization, DFT simulation and biological assays of two new metal complexes of 2-(2-thi- enyl)benzothiazole – BTT are reported. The complexes [Ag(BTT) 2 NO 3 ] – AgBTT 2 and [Au(BTT)Cl]½H 2 O– AuBTT were obtained by mixing the ligand with silver (I) nitrate or gold(I) chloride in methanolic solution. Characterization of the complexes were based on elemental (C, H, N and S), thermal (TG-DTA) analysis, 13 C and 1 H NMR, FT-IR and UV–Vis spectroscopic measurements, as well as the X-ray structure determination for AgBTT 2 . Spectroscopic data predicted by DFT calculations were in agreement with the experimental data for both complexes. The ligand BTT was synthesized by the condensation of 2-thiophenecarboxalde- hyde and 2-aminothiophenol in a microwave furnace. AgBTT 2 has a monomeric structure. Both complexes show a good activity against Mycobacterium tuberculosis. Free BTT shows low antitubercular activity. Ó 2012 Elsevier Ltd. All rights reserved. 1. Introduction Elemental silver and its compounds have been used as antibac- terial agents for a century as therapeutic compounds [1]. A few silver(I) compounds have been prescribed because of their topical anti-bacterial effects. For example, silver sulfadiazine (SSD) is widely used for burn treatment and diluted solution of AgNO 3 is employed to prevent bacterial infections and conjunctivitis in new- borns [2–5]. The chemistry of gold-based drugs has also been explored for a long time and commercial compounds such as AuranofinÓ, solganolÓ and myochrisineÓ are a good sample of medicines based on gold(I) compounds used for treatment of rheumatoid arthritis that seems to alleviate the pain caused by the disease improving wellness of patients [6]. On the other hand, the use of metals and its salts as antimicro- bial agents declined sharply in the middle of the last century upon the introduction of antibiotics. Since microorganisms, virus and tumors still represent a menace to the public health, research in the sense to develop and optimize new drugs are always of interest of the society. Tuberculosis (TB), for example, remains as a public health issue in the beginning of the 21st century. TB causes nearly 3 million deaths annually worldwide. There are estimated 8.8 mil- lion of new cases corresponds to 52 000 deaths per week or more than 7000 deaths each day. In the developing countries TB is a lead- ing cause of morbidity and mortality. Co-infections with human immunodeficiency virus (HIV) have been responsible for changes in the TB epidemiologic situation leading multi-drug resistant strains [7]. With the ever increasing problem of microbe resistance to current antimicrobial agents, particularly antibiotics, there is an urgent demand for new classes of compounds that will efficiently inhibit the growth of pathogenic microorganisms. Due to this crit- ical situation, an intense effort is being addressed to develop new drugs against microorganisms or virus, particularly against Myco- bacterium tuberculosis. Currently, there is a strong interest in 0277-5387/$ - see front matter Ó 2012 Elsevier Ltd. All rights reserved. http://dx.doi.org/10.1016/j.poly.2012.03.016 Abbreviations: NMR, nuclear magnetic resonance; t, triplet; d, duplete; TG/DTA, thermogravimetric/differential thermal analysis; UV–Vis, ultraviolet/visible; BTT, 2- (2-thienyl)benzothiazole; AgBTT 2 , silver complex with 2-(2-thienyl)benzothiazole; AuBTT, gold(I) complex with 2-(2-thienyl)benzothiazole; MIC, minimal inhibitory concentration; ATCC, American type collection cell; 7H9, broth used to growth mycobacterial species; DMSO, dimethylsulfoxide; CDCl 3 , chloroform-d; DFT, Den- sity functional theory; LANL2DZ, Los Alamos National Laboratory – 2nd version on double zeta function; B3LYP, Becke 3-Lee Yang Parr functional; TD, time dependent method; CCDC, Cambridge Crystallographic Data Centre; HOMO/LUMO, highest occupied/lowest unoccupied molecular orbital. ⇑ Corresponding author. Tel.: +55 32 3229 3310. E-mail addresses: alexandre_cuin@yahoo.com, alexandre.cuin@ufjf.edu.br (A. Cuin). Polyhedron 38 (2012) 291–296 Contents lists available at SciVerse ScienceDirect Polyhedron journal homepage: www.elsevier.com/locate/poly