Novel Pyran-Linked Phthalazinone-Pyrazole Hybrids: Synthesis, Cytotoxicity Evaluation, Molecular Modeling, and Descriptor Studies

Abstract

A series of novel pyran-linked phthalazinone-pyrazole hybrids were designed and synthesized by a facile one-pot three-component reaction employing substituted phthalazinone, 1H-pyrazole-5-carbaldehyde, and active methylene compounds. Optimization studies led to the identification of L-proline and ethanol as efficient catalyst and solvent, respectively. This was followed by evaluation of anticancer activity against solid tumor cell lines of lung and cervical carcinoma that displayed IC50 values in the range of 9.8–41.6 µM. Molecular modeling studies were performed, and crucial interactions with the target protein were identified. The drug likeliness nature of the compounds and molecular descriptors such as molecular flexibility, complexity, and shape index were also calculated to understand the potential of the synthesized molecules to act as lead-like molecule upon further detailed biological investigations as well as 3D-QSAR studies.

Inhibitory potential of nitrogen, oxygen and sulfur containing heterocyclic scaffolds against acetylcholinesterase and butyrylcholinesterase

“…The crystal structure of AChE has revealed the shape and mechanism of action of the enzyme. [140][141][142][143][144][145][146][147][148][149][150] AChE is one of the most important enzymes in the serine hydrolase family, as it is engaged in the cleavage of ACh, exhausting ACh levels linked to memory and learning. 151 As a result, the cholinergic hypothesis for cognition problems implies that degeneration in ACh-containing neurons play a signicant role in the cognitive decline linked to old age.…”

Novel cis‐Pt(II) Complexes with Alkylpyrazole Ligands: Synthesis, Characterization, and Unusual Mode of Anticancer Action

“…However, a search in the literature has yielded several references suggesting that pyrazoles and their derivatives, such as dihydropyrazole, are widely recognized as potent inhibitors of Eg5 [49][50][51][52].…”

Antibacterial Properties and Computational Insights of Potent Novel Linezolid-Based Oxazolidinones

“…In addition to this, several research groups have designed new oxazolidinone derivatives and evaluated their antibacterial potency, with good degrees of success [15][16][17][18]. In view of our research interest in the development of new bioactive compounds [19][20][21][22][23], we recently reported the design and synthesis of novel linezolid-based oxazolidinones as anticandidal and antitubercular agents [24]. In our previous study, the lead molecule (linezolid 1) was modified by the replacement of thiomorpholine with N-sulphonyl piperazine moiety, incorporation of a 2-nitrofuranamide group and the replacement of acetamide with heteryl and biphenylacryl amides.…”