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Microtubule affinity-regulating kinase 4 (MARK4), a member of the serine/threonine kinase family, is an emerging therapeutic target in anticancer drug discovery paradigm due to its involvement in regulation of microtubule dynamics, cell cycle regulation, and cancer progression. Therefore, to identify the novel chemical architecture for the design and development of novel MARK4 inhibitors with concomitant radical scavenging property, a series of small-molecule arylaldoxime/5-nitroimidazole conjugates were designed and synthesized via multistep chemical reactions following the pharmacophoric hybridization approach. Compound 4h was identified as a promising MARK4 inhibitor with high selectivity toward MARK4 inhibition as compared to the panel of screened 30 kinases pertaining to the serine/threonine family, which was validated by molecular docking and fluorescence binding studies. The comprehensive cell-based examination divulged the promising apoptotic, antiproliferative, and antioxidant potential for the chemotype 4h . The compound 4h was endowed with the K a value of 3.6 × 10 3 M –1 for human serum albumin, which reflects its remarkable transportation and delivery properties to the target site via blood. The present study impedes that in the future, such compounds may stand as optimized pharmacological lead candidates in drug discovery for targeting cancer via MARK4 inhibition with a remarkable anticancer profile.

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Reaction of trans-[PdCl 2 (DMSO) 2 ], cis-[PtCl 2 (DMSO) 2 ], and [Cu(OAc) 2 ] ¥ H 2 O with metronidazole (mnz) leads to the formation of new complexes, i.e., trans-[PdCl 2 (mnz) 2 ] (1), trans-[PtCl 2 (mnz) 2 ] (2), and trans-[Cu 2 (OAc) 4 (mnz) 2 ] (3), respectively. Complexes 1 ± 3 crystallize all in the centrosymmetric monoclinic space group P2 1 /c with Z 8. Unit-cell parameters for these complexes are: 1, a 7.1328(14) ä, b 20.699(4) ä, c 7.1455(14) ä, and b 116.17(3)8; 2, a 6.9169(14) ä, b 21.853(4) ä, c 6.7218(13) ä, and b 110.79(3)8; 3, a 9.1663(18) ä, b 19.129(4) ä, c 8.9446(18) ä, and b 116.44(3)8. The complexes 1 and 2 maintain an ideal square-planar geometry. In complex 3, the H 2 O molecules of the starting complex are replaced by metronidazole while maintaining a dimeric structure of [Cu(OAc) 2 ]. Each Cu ion has an ideal octahedral structure, though distortion occurs in the equatorial position where the acetato ligands are attached. The CuÀCu separation of 2.6343(8) ä indicates considerable metal-metal interaction.The testing of the antiamoebic activity of these complexes against the protozoan parasite Entamoeba histolytica suggests that compound 1 ± 3 might be endowed with important antiamoebic properties since they showed IC 50 values in a mm range better than metronidazole (Table 2). Thus, compound 1 displayed more effective amoebicidal activity than metronidazole (IC 50 values of 0.103 mm vs. 1.50 mm, resp.).