Synthesis of isatin thiosemicarbazones derivatives: In vitro anti-cancer, DNA binding and cleavage activities Amna Qasem Ali a , Siang Guan Teoh a,⇑ , Abdussalam Salhin a , Naser Eltaher Eltayeb b , Mohamed B. Khadeer Ahamed c , A.M.S. Abdul Majid c a School of Chemical Sciences, Universiti Sains Malaysia, Minden 11800, Pulau Pinang, Malaysia b Department of Chemistry, Sciences & Arts College – Rabigh, King AbdullAziz University, Rabigh, Saudi Arabia c EMAN Research and Testing Laboratory, School of Pharmaceutical Sciences, Universiti Sains Malaysia, Minden 11800, Pulau Pinang, Malaysia highlights  New derivatives of thiosemicarbazone Schiff base with isatin moiety were synthesized.  The interaction of these compounds with calf thymus CT-DNA exhibited high intrinsic binding constant.  The electrophoresis studies show the higher cleavage activity of L1–L3.  Compounds (L3, L6 and L2) exhibited good anticancer activity. graphical abstract article info Article history: Received 5 November 2013 Received in revised form 16 January 2014 Accepted 20 January 2014 Available online 29 January 2014 Keywords: Thiosemicarbazone Isatin moiety CT-DNA binding DNA cleavage In vitro anti-proliferative activity abstract New derivatives of thiosemicarbazone Schiff base with isatin moiety were synthesized L1–L6. The struc- tures of these compounds were characterized based on the spectroscopic techniques. Compound L6 was further characterized by XRD single crystal. The interaction of these compounds with calf thymus (CT-DNA) exhibited high intrinsic binding constant (k b = 5.03–33.00  10 5 M 1 ) for L1–L3 and L5 and (6.14–9.47  10 4 M 1 ) for L4 and L6 which reflect intercalative activity of these compounds toward CT-DNA. This result was also confirmed by the viscosity data. The electrophoresis studies reveal the higher cleavage activity of L1–L3 than L4–L6. The in vitro anti-proliferative activity of these compounds against human colon cancer cell line (HCT 116) revealed that the synthesized compounds (L3, L6 and L2) exhibited good anticancer potency. Ó 2014 Elsevier B.V. All rights reserved. Introduction Isatin (1H-indole-2,3-dione) was first discovered by Erdmann and Laurent in 1840 as a product of indigo oxidation [1,2]. Isatin have also been recognized in natural products, such as in humans as it is a metabolic derivative of adrenaline, marine molluscs, fungal metabolites and in the fruits of the cannon ball tree [3–5]. The syn- thetic ingenuity of isatin has led to the wide use of this compound in organic synthesis which reported to possess a variety of pharmaco- logical properties such as anti-viral activities, antibacterial, antican- cer activities, anticonvulsant activity, cytotoxicity antioxidant activity [6–17]. Hence our studies have been focused towards the synthesis of a series of isatin thiosemicarbazone derivatives with empirical formula, C 15 H 12 N 4 OS (L1), C 16 H 14 N 4 OS (L2), C 15 H 11 FN 4 OS (L3), C 10 H 9 N 5 O 3 S (L4), C 11 H 12 N 4 OS (L5) and C 12 H 14 N 4 OS (L6). http://dx.doi.org/10.1016/j.saa.2014.01.086 1386-1425/Ó 2014 Elsevier B.V. All rights reserved. ⇑ Corresponding author. Tel.: +60 4 6577888x3565; fax: +60 4 6574854. E-mail address: sgteoh@usm.my (S.G. Teoh). Spectrochimica Acta Part A: Molecular and Biomolecular Spectroscopy 125 (2014) 440–448 Contents lists available at ScienceDirect Spectrochimica Acta Part A: Molecular and Biomolecular Spectroscopy journal homepage: www.elsevier.com/locate/saa