Schiff bases of indoline-2,3-dione (isatin) with potential antiproliferative activity

Abstract

BackgroundCancer is one of the most dreaded diseases and it is a leading cause of mankind death worldwide. Recent reports documented a remarkable antiproliferative activity of isatin nucleus against various cancer cell lines. The current work describes the antiproliferative activity of Schiff bases of combinatorial mixtures of the isatin derivatives M1-M22 as well as the individual compounds 1-11(A-K) of these combinatorial mixtures.ResultsThe designed combinatorial library composed from eleven hydrazides A-K and eleven isatin derivatives 1-11 has been synthesized to formally generate 22 mixtures, M1-M22 of 121 Schiff bases, and their antiproliferative activity against K562 chronic myelogenous leukemia cells was evaluated. The indexed method of analysis of the prepared library was applied to elucidate the active components in the tested mixtures M1-M22. The predictions from the crossing procedure was validated through evaluation of the antiproliferative activity of individual compounds 1-11(A-K) of the library. Individual compounds 1-11(A-K) were also evaluated against the non-tumorigenic MCF-12A cell line to investigate their selectivity. A pharmacophore model was developed to further optimize the antiproliferative activity among this series of compounds.ConclusionsVariable antiproliferative activity was revealed with the investigated mixtures M1-M22 and the individual compounds 1-11(A-K). Most of the tested mixtures and several individual Schiff bases displayed high potency with IC50 values in the low micromolar range. A considerable selectivity of some individual compounds to the tumorigenic K562 cell line compared with the non-tumorigenic MCF-12A cell line was observed as indicated by their selectivity index (SI).

Design, synthesis and QSAR study of certain isatin-pyridine hybrids as potential anti-proliferative agents

“…The present study is an extension of our ongoing efforts towards developing potent isatin-based anticancer agents [35,36,[45][46][47], utilizing a hybrid pharmacophore approach. In view of the previous findings, we decided to design and synthesize three different set of isatin-pyridine hybrids 5a-o, 8 and 11a-d (Figure 1), with the prime aim of developing potent anticancer agents.…”

Synthesis and in vitroAntimicrobial Activity of Nalidixic Acid Hydrazones

“…Furthermore, a number of hydrazone derivatives have been claimed to possess other interesting activities like anticancer [7,8], anti-inflammatory [9,10], antibacterial [11,12], antifungal [13], and antitubercular activity [14,15].…”

Isatin Derivatives with Potential Antitubercular Activities

“…The sparfloxacin‐isatin hybrids 21 also demonstrated considerable activities (MIC <6.25 μg/mL) against MTB H37Rv, but less potent than the parent sparfloxacin (MIC: 0.5 μg/mL) . Several carbohydrazide tethered nalidixic acid‐isatin conjugates 22 were screened for their in vitro activities against Mycobacterium intercellulari , Mycobacterium xenopi , Mycobacterium cheleneo , and M. smegmatis by Aboul‐Fadl et al . Most of them showed promising activities with MIC in a range of 0.09 to 0.625 μg/mL, which were far more potent than INH (MIC: 12.5 μg/mL).…”