Original article A facile synthesis of carbocycle-fused mono and bis-1,2,3-selenadiazoles and their antimicrobial and antimycobacterial studies Selvam Chitra a , Nidhin Paul b , Shanmugam Muthusubramanian b, * , Paramasivam Manisankar a, ** , Perumal Yogeeswari c , Dharmarajan Sriram c a Department of Industrial Chemistry, Alagappa University, Karaikudi 630 003, Tamil Nadu, India b Department of Organic Chemistry, School of Chemistry, Madurai Kamaraj University, Madurai 625 021, Tamil Nadu, India c Medicinal Chemistry & Antimycobacterial Research Laboratory, Pharmacy Group, Birla Institute of Technology & Science e Pilani, Hyderabad Campus, Jawahar Nagar, Hyderabad 500 078, Andhra Pradesh, India article info Article history: Received 3 August 2011 Received in revised form 27 August 2011 Accepted 6 September 2011 Available online 10 September 2011 Keywords: Oxidative cyclization 1,2,3-Selenadiazole Antimicrobial activity Mycobacterium tuberculosis abstract A series of mono and bis-1,2,3-selenadiazole derivatives have been synthesized by the oxidative cyclization of mono and bis semicarbazones of 2-(3-oxo-1,3-diarylpropyl)-1-cyclohexanones using selenium(IV) oxide. The newly synthesized compounds were evaluated for their in vitro antimicrobial activity against Escher- ichia coli (ATCC 25922), Staphylococcus aureus (ATCC 11632) and Candida albicans (ATCC 90028) and in vitro antituberculosis activity against Mycobacterium tuberculosis H37Rv (MTB). Among these compounds, 1,3- di(4-chlorophenyl)-3-(4,5,6,7-tetrahydro-1,2,3-benzoselenadiazol-4-yl)-1-propanone (2h) and 3-(4-chlor- ophenyl)-1-(4-methylphenyl)-3-(4,5,6,7-tetrahydro-1,2,3-benzoselenadiazol-4-yl)-1-propanone (2g) were found to be the most active compounds with MIC of 3.3 and 3.5 mM respectively against MTB. Ó 2011 Elsevier Masson SAS. All rights reserved. 1. Introduction Infectious diseases have been serious and growing threat to human health during the past few decades [1,2]. The decrease of sensibility to antimicrobial agents of current use has also been increasing for a great variety of pathogens, especially for Gram- positive bacteria [3] and some intractable fungi [4]. The alarming rates of emerging microbial threats are major concerns to the public health and scientific communities worldwide [5]. Similarly Myco- bacterium tuberculosis (MTB) is responsible for the death of around 2e3 million people annually and the statistics shows that around 32% of the world’s population is infected by Mycobacterium tuber- culosis, the main causal agent of TB and today more people die from tuberculosis than ever before [6]. WHO has estimated that 9.2 million new incident cases in 2006, with approximately 1.7 million individual deaths in the same year, and one-third of the world population is latently infected with MTB. The deadly synergy with HIV [7,8], the development and spread of multidrug-resistant strains of MTB (MDR-TB) [9e11] and the emergence of exten- sively drug resistant MTB strains (XDR-TB) [7] are the reasons pointed out for the increased number of infections. The above points clearly indicate the need for the synthesis of new compounds with possible antimicrobial and antituberculosis activities. Selenium containing heterocyclic systems are of interest due to their potential pharmaceutical properties [12e15] and some of them are used as chemotherapeutic agents [16]. Among selenium con- taining heterocyclic compounds, 1,2,3-selenadiazoles and their derivatives have attracted attention as versatile synthetic interme- diates [17]. Many substituted 1,2,3-selenadiazoles show high anti- bacterial activity [18]. The antifungal activity of some substituted 1,2,3-selenadiazoles has also been determined [12b,13,19]. It has been found that the introduction of a 1,2,3-selenadiazole ring to molecules of known biologically active compounds changes their activities and in some cases leads to an increase in their biological action [20]. 1,2,3- Selenadiazoles also exhibit other biological activities, including anticipated antitumor [21], antimicrobial [22], antiaflatoxigenic [23], antihaemostatic [24] and insecticidal activities [25]. There is a surprise lack of literature on their antitubercular activity against Mycobacterium tuberculosis (MTB) by this class of compounds. In continuation of our study on generating new heterocyclic compounds [26] and their possible biological activity [27], in this * Corresponding author. Tel./fax: þ91 452 2459845. ** Corresponding author. E-mail addresses: muthumanian2001@yahoo.com (S. Muthusubramanian), pms11@rediffmail.com (P. Manisankar). Contents lists available at SciVerse ScienceDirect European Journal of Medicinal Chemistry journal homepage: http://www.elsevier.com/locate/ejmech 0223-5234/$ e see front matter Ó 2011 Elsevier Masson SAS. All rights reserved. doi:10.1016/j.ejmech.2011.09.007 European Journal of Medicinal Chemistry 46 (2011) 5465e5472