ORIGINAL PAPER Synthesis and biological evaluation of 1,3,4-oxadiazole-linked bisindole derivatives as anticancer agents Islavathu Hatti • Reddymasu Sreenivasulu • Surender Singh Jadav • Mohamed Jawed Ahsan • Rudraraju Ramesh Raju Received: 26 December 2014 / Accepted: 25 February 2015 Ó Springer-Verlag Wien 2015 Abstract A series of ten 1,3,4-oxadiazole-linked bisin- dole derivatives have been synthesized. All compounds were evaluated for anticancer activity against four human cancer cell lines (MCF-7, KB, Colo-205, and A-549). Most of these new compounds exhibited significant anticancer activity as compared to etoposide. Compounds’ GI 50 values range from \ 0.1 to 3.9 lM, while the positive control etoposide has a GI 50 in the range of 0.13–3.08 lM in the cell lines employed. Among them, four compounds showed a higher activity than etoposide. Graphical abstract N N CHO OCH3 N N O HN O NH2 CO2H R N N O O N N R + Keywords Nortopsentins A-C  Hamacanthin B  Zibotentan (ZD4054)  Bisindoles  1,3,4-Oxadiazoles  Cytotoxicity Introduction Cancer is the second leading cause of mortality in devel- oped countries. Currently, chemotherapy is the most important treatment for cancer and the ultimate goal is to destroy the cancer cells without any harmful effect on the normal cells. Within the past decade, advances in our un- derstanding of the cell cycle have presented new targets that may allow for the development of more selective chemotherapeutic agents—agents that target only cancer cells. Cancer chemotherapy has achieved significant suc- cess through the discovery of various new drugs. Despite of this progress, the discovery of most potent anticancer agents is a challenging issue in cancer chemotherapy for the future generations. The indole fragment is featured widely in a variety of therapeutic agents with different pharmacological activities, such as anticancer [1], antioxidant [2], antirheumatoidal [3], and anti-HIV [4, 5]. Recently, bisindole alkaloids consisting of two indole moieties bound to a spacer through their third position were found to exhibit a wide spectrum of potent biological activities including antifungal, antitumor, antivi- ral, antimicrobial, anti-inflammatory, and cytotoxic activities [6–11]. The bisindole alkaloids can bear either an acyclic chain or six-membered carbocyclic or five-mem- bered heterocyclic ring or six-membered heterocyclic ring between two indole rings. The 2,4-bis(3 0 -indolyl)imidazole (Nortopsentins A-C, 1)[12] exhibit in vitro cytotoxicity against P388 cells, and 3,5-bis(3 0 -indolyl)pyrazinone (Ha- macanthin B, 2) [13, 14] (Fig. 1), exhibits cytotoxic I. Hatti  R. Sreenivasulu  R. R. Raju (&) Department of Chemistry, Acharya Nagarjuna University, Nagarjuna Nagar 522 510, Andhra Pradesh, India e-mail: rrraju1@gmail.com S. S. Jadav (&) Department of Pharmaceutical Sciences and Technology, Birla Institute of Technology, Mesra, Ranchi 835 215, Jharkhand, India e-mail: surenderjs@gmail.com M. J. Ahsan (&) Department of Pharmaceutical Chemistry, Maharishi Arvind College of Pharmacy, Jaipur 302 023, Rajasthan, India e-mail: jawedpharma@gmail.com 123 Monatsh Chem DOI 10.1007/s00706-015-1448-1