Synthesis, computational studies and biological activity of oxamohydrazide derivatives bearing isatin and ferrocene scaffolds

Ferrocene-based anti-inflammatory drug discovery has become an important area in medicinal chemistry. Utilizing the condensation of isatin or ferrocene carbaldehyde with nucleophile, such as oxamic acid hydrazide, the desired isatin 1, and ferrocene 2 oxamohydrazide derivatives were smoothly synthesized in high purity and yield. The structures of the isatin, and ferrocene oxamohydrazides were elucidated using single crystal X-ray diffraction technique, and DFT calculations. Hirshfeld analysis sheds the light on the importance of the O center dot center dot center dot H hydrogen bonds in the molecular packing in both compounds. The oxamohydrazides were examined for anti-inflammatory, and anti-leishmanial activities. The ferrocene oxamohydrazide analogue 2, (IC50 = 5.7 +/- 0.3 mu M) exhibited a potent anti-inflammatory effect, and was two times more active than the tested ibuprofen as control (IC50 = 11.2 +/- 1.9 mu M). (C) 2019 Elsevier B.V. All rights reserved.