An efficient one-pot synthesis and docking studies of bioactive new antiproliferative dispiro[oxindole/acenaphthylenone‒benzofuranone] pyrrolidine scaffolds.

A new and efficient method has been developed to synthesize dispiro[oxindole/acenaphthylenone-benzofuranone]pyrrolidine compounds. This is done by triggering the 1,3-dipolar cycloaddition reaction of azomethine ylides by reacting isatin/acenaphthoquinone with L-picolinic acid/L-proline/sarcosine/L-thioproline/tetrahydroisoquinolines, in a highly regioselective manner in an ionic liquid [DBU][Ac] with 4'-chloro-auron[2-(4-chlorobenzylidene)benzofuran-3(2H)-one]. Single-crystal X-ray diffraction data support the proposed structures of the new compounds. The heterocycles derived from amino acids such as L-picolinic acid, L-proline, and L-thioproline showed significant inhibitory effects against six human solid tumors, including lung, breast, cervix, colon, and others. These new structures were also tested in the active sites of the MDM2 receptor to further study their antiproliferative effects.

Benzylpiperidine-Linked Diarylthiazoles as Potential Anti-Alzheimer's Agents: Synthesis and Biological Evaluation.

A novel series of hybrid molecules were designed and synthesized by fusing the pharmacophoric features of cholinesterase inhibitor donepezil and diarylthiazole as potential multitarget-directed ligands for the treatment of Alzheimer's disease (AD). The compounds showed significant in vitro anticholinesterase (anti-ChE) activity, the most potent compound (44) among them showing the highest activity (IC50 value of 0.30 ± 0.01 µM) for AChE and (1.84 ± 0.03 µM) for BuChE. Compound 44 showed mixed inhibition of AChE in the enzyme kinetic studies. Some compounds exhibited moderate to high inhibition of AChE-induced Aß1-42 aggregation and noticeable in vitro antioxidant and antiapoptotic properties. Compound 44 showed significant in vivo anti-ChE and antioxidant activities. Furthermore, compound 44 demonstrated in vivo neuroprotection by decreasing Aß1-42-induced toxicity by attenuating abnormal levels of Aß1-42, p-Tau, cleaved caspase-3, and cleaved PARP proteins. Compound 44 exhibited good oral absorption and was well tolerated up to 2000 mg/kg, po, dose without showing toxic effects.

Medicinal Chemistry Perspective of Fused Isoxazole Derivatives.

Nitrogen containing heterocyclic rings with an oxygen atom is considered as one of the best combination in medicinal chemistry due to their diversified biological activities. Isoxazole, a five membered heterocyclic azole ring is found in naturally occuring ibetonic acid along with some of the marketed drugs such as valdecoxib, flucloxacillin, cloxacillin, dicloxacillin, and danazol. It is also significant for showing antipsychotic activity in risperidone and anticonvulsant activity in zonisamide, the marketed drugs. This review article covers research articles reported till date covering biological activity along with SAR of fused isoxazole derivatives.