Synthesis, Cytotoxic and Phytotoxic Effects of Some New N4-Aryl Substituted Isatin-3-thiosemicarbazones

Abstract

A series of N 4 -aryl substituted isatin-3-thiosemicarbazones was prepared by the reaction of isatin with an appropriate thiosemicarbazide in ethanol containing a few drops of acetic acid. The newly synthesized compounds were characterized by means of their analytical (CHN) and spectral (IR, 1 H-NMR, EIMS) data, and evaluated for their cytotoxicity and phytotoxicity potential. Eleven out of thirteen compounds tested proved to be active in the brine-shrimp lethality bioassay exhibiting significant cytotoxic activity with LD 50 values ranging from 1.75x10 -5 M to 1.91x10 -4 M. In phytotoxicity assay, all the synthesized compounds, regardless of the nature of aryl substituents, demonstrated weak to moderate (5-30%) plant growth inhibition at the highest tested concentration (500 μg/mL).

(Z)-4-(3-Fluorophenyl)-1-(5-nitro-2-oxoindolin-3-ylidene)thiosemicarbazide

“…Data collection: APEX2 (Bruker, 2007); cell refinement: SAINT (Bruker, 2007); data reduction: SAINT; program(s) used to solve structure: SHELXS97 (Sheldrick, 2008); program(s) used to refine structure: SHELXL97 (Sheldrick, 2008); molecular graphics: ORTEP-3 for Windows (Farrugia, 1997) and PLATON (Spek, 2009); software used to prepare material for publication: WinGX (Farrugia, 1999) and PLATON. In continuation of our earlier studies on some isatins-thiosemicarbazones (Pervez et al 2010;Pervez, Ramzan et al, 2011;Pervez, Saira et al, 2011), we report herein the structure and synthesis of the title compound (I), (Fig. 1).…”

“…For background to isatin derivatives, see: Pervez et al (2010); Pervez, Ramzan et al (2011); Pervez, Saira et al (2011). For related structures, see: Pervez et al (2009); Ramzan et al (2010).…”

Recent Highlights in the Development of Isatin-Based Anticancer Agents

“…Analogue 44c was the most active in the series, exhibiting an IC 50 value of 0.8 µM against Shp2. In recent years, Pervez and co-workers have reported the cytotoxic activity of isatin derivatives containing a thiosemicarbazone moiety (a hydrazone derivative containing a sulfur atom) [125][126][127][128].…”

Synthesis and in vitro Bio-activity Evaluation of N4-benzyl Substituted 5-Chloroisatin- 3-thiosemicarbazones as Urease and Glycation Inhibitors

“…Of the isatin derivatives, isatin-thiosemicarbazones have been found to exhibit a range of biological properties, including antiulcer, 1 anticancer, 1,4,7,12,[21][22][23] antimicrobial, [1][2][3]5,7,22,24,25 antituberculosis, [26][27][28] antiviral 1,2,5,7,12,28 and enzyme inhibitory activities. 1,4,11,17 Incited by these findings and as a part of our synthetic work on bioactive isatin derivatives, we have recently reported the synthesis of numerous N 4 -aryl substituted isatin-3-thiosemicarbazones (thiourea derivatives) as antimicrobial, [36][37][38][39] cytotoxic, [38][39][40][41][42] phytotoxic, [38][39][40][41]43 antileishmanial 44 and more importantly antiurease [36][37][38][39][40]…”

“…SAR studies in the synthesized thiosemicarbazones disclosed that in some cases the nature and location of the substituent on the phenyl ring attached to thiosemicarbazone N 4 and/or the existence of lipophilic/inductively electron-withdrawing functions (Cl, F, F 3 CO, NO 2 ) at position 5 of the isatin moiety played a significant role in inducing and/or increasing certain activities, including urease inhibition. In view of this and as an extension of our earlier studies [36][37][38][39][40][41][42][43][44][45][46][47] aiming to the synthesis of novel isatin derivatives with enhanced or diverse biological activities, we very recently reported the synthesis of a series of N 4 -benzyl substituted 5-nitroisatin-3-thiosemicarbazones (derivatives of thiourea, a substrate-like urease inhibitor) as highly effective urease inhibitors. 48 Interestingly, all these compounds demonstrated either induced or increased urease inhibitory activity in comparison to the respective N 4 -phenyl substituted derivatives tested in our earlier assays.…”