Synthesis, in vitro anticancer and antimycobacterial evaluation of new 5-(2,5-dimethoxyphenyl)-1,3,4-thiadiazole-2-amino derivatives Naveen Polkam a , Parsharamulu Rayam a , Jaya Shree Anireddy a,⇑ , Satyanarayana Yennam b , Hasitha Shilpa Anantaraju c , Sriram Dharmarajan c , Yogeeswari Perumal c , Sudha Sravanti Kotapalli d , Ramesh Ummanni d , Sridhar Balasubramanian e a Centre for Chemical Sciences and Technology, IST, Jawaharlal Nehru Technological University Hyderabad, Kukatpally, Hyderabad 500085, T.S., India b Department of Medicinal Chemistry, GVK Biosciences Pvt. Ltd, IDA, Nacharam, Hyderabad 500076, T.S., India c Department of Pharmacy, Birla Institute of Technology and Science, Pilani, Hyderabad Campus, Jawahar Nagar 500078, T.S., India d Center for Chemical Biology, CSIR-Indian Institute of Chemical Technology, Tarnaka, Hyderabad 500007, T.S., India e Laboratory of X-ray Crystallography, CSIR-Indian Institute of Chemical Technology, Tarnaka, Hyderabad 500007, T.S., India article info Article history: Received 15 December 2014 Revised 7 February 2015 Accepted 20 February 2015 Available online 27 February 2015 Keywords: Anti-mycobacterial activity Cytotoxic activity 2,5-Disubstitued-1,3,4-thiadiazole In vitro studies MTT colorimetric assay abstract A series of 2,5-disubstituted-1,3,4-thiadiazole derivatives 5a–5l, 7a–7e and 9 have been synthesised and screened for in vitro antimycobacterial activity against Mycobacterium smegmatis MC-155. In addition these compounds have also been screened for cytotoxic activity against cancer cell lines HT-29, MDA- MB-231 by MTT colorimetric assay. The compounds are well characterized by spectral analysis viz. 1 H NMR, 13 C NMR, FT-IR, mass and HRMS. Screening results indicate that compounds 5g, 7a possess good antitubercular activity with MIC value 65.74 and 40.86, respectively, compounds 5g, 7a, 7b, 7d, 7e and 9 displayed promising cytotoxic activity against the cell lines tested. 5g and 7a stand out to be potent antimycobacterial and anticancer agents among the tested series. Further the title compounds were also tested on human normal cells HEK293T and are found to be safer with lesser cytotoxicity. It is interesting to observe that compound 5g has come out to be safer, potent anticancer and antimycobacterial agent. Ó 2015 Elsevier Ltd. All rights reserved. Now-a-days agents for the treatment of cancer and mycobacte- rial infections have drawn special interest from medicinal chem- istry point of view. Tuberculosis (TB) is one among the major infectious diseases caused by Mycobacterium tuberculosis and pri- marily affects lungs as well as kidneys and brain. 1,2 It is estimated that 9.0 million people are affected globally by TB infection with 1.5 million deaths 3 and declared as global public health crisis by WHO. 4–6 The multifold resistance acquired by these organisms, necessitates design of newer antibacterials. Tuberculosis seems to conglomerate tuberculomas which are the clinical manifestation of infection caused by Mycobacterium. 7 Perhaps tuberculoma is identified as one of the oldest cause of cancer and can affect organs such as brain, 8 ovaries, 9 breast, 10 lungs, 11 esophagus, 12 intestine, 13 pancreas, 14 bones, 15 etc. Hence, interest is being increased on alter- native therapies to develop drugs with multi-pronged mode of action. Drugs having broad spectrum cytotoxicity ranging from prokaryotes to eukaryotes compliment the strategic treatment for cancer as well as tuberculosis and prove beneficial in certain cases. Cancer, the uncontrolled division of cells is a global chal- lenge in the present scenario. 16 The pursuit for the newer anti- cancer agents with fewer or no side effects became the focal point of the current research. 17 Heterocyclic compounds are of special interest to medicinal chemists because of their exceptional chemical and versatile biolo- gical profiles. Despite significant research progress on heterocyclic ring systems, efforts are on-going to identify novel heterocyclic compounds with potent bioactivities. The 1,3,4-thiadiazole frame work, a well-known heterocyclic scaffold has drawn special interest because of its inherent and diverse biological response. 18 The molecule was first described by Fischer in the year 1882 and was further developed by Busch and co-workers. 19 Thiadiazole is a 5-membered planar aromatic 20 motif featuring sulfur atom which improves the lipid solubility, 21 hence the pharmaco kinetics. The two-electron donor nitrogen system (AN@CAS) and hydrogen- binding domain helps in pharmaco dynamics of the molecule for better binding with the receptor/s. 19,20 Thiadiazoles are bioisosteres 19,20 of pyrimidines, oxadiazoles, oxazoles, benzene and its derivatives have been reported to display diverse range of biological and pharmacological properties such as antimicrobial, 22 http://dx.doi.org/10.1016/j.bmcl.2015.02.052 0960-894X/Ó 2015 Elsevier Ltd. All rights reserved. ⇑ Corresponding author. Tel.: +91 040 2315 6128; fax: +91 040 2305 8729. E-mail address: jayashreeanireddy@gmail.com (J.S. Anireddy). Bioorganic & Medicinal Chemistry Letters 25 (2015) 1398–1402 Contents lists available at ScienceDirect Bioorganic & Medicinal Chemistry Letters journal homepage: www.elsevier.com/locate/bmcl