A comprehensive investigation of 4-(4-chlorophenyl)-3-methyl-6,7,8,9-tetrahydroisoxazolo[5,4-b]quinolin-5(4H)-one as potential anticancer agent: insights from computational and experimental results through crystal structure analysis

Darshini, G. and Vinay Kumar, D. C. and Byresh, G. and Chethan, B. S. and Harsha, K. B. and Shalini, V. and Sudhanva, M. S. and Shobith, R. and Rangappa, K. S. (2025) A comprehensive investigation of 4-(4-chlorophenyl)-3-methyl-6,7,8,9-tetrahydroisoxazolo[5,4-b]quinolin-5(4H)-one as potential anticancer agent: insights from computational and experimental results through crystal structure analysis. Journal of Molecular Structure, 1330. ISSN 0022-2860

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Abstract

The quest for effective, less-toxic medications for colon and pancreatic cancer is one of the most important problems being faced by modern pharmacy and medicine. In this context, synthesis of 4-(4-chlorophenyl)-3- methyl-6,7,8,9-tetrahydroisoxazolo[5,4-b] quinolin-5(4H)-one (CPIQ) compound from multicomponent reaction is achieved by using T3P®-DMSO-catalyzed reaction via a tandem oxidative–condensation reaction under mi- crowave irradiation. In this extended work, we have crystallized the compound and investigated its several properties using ab-initio, in-silico and in-vitro methods. The compound characterizations are carried out through the spectroscopic methods (FTIR, UV–vis, LCMS, NMR) in order to confirm the formation of the crystal. The single crystal X-ray diffraction study is used to define the crystal structure, the CIPQ compound crystallizes in triclinic crystal system with P1 space group. Several intra-, intermolecular, and π⋅⋅⋅π interactions are observed due to C–H⋅⋅⋅H, C–H⋅⋅⋅C, C–H⋅⋅⋅O, and C–O⋅⋅⋅H contacts in the synthesized molecule, which is further corroborated with Hirshfeld surface analysis and QTAIM based NCI-RDG isosurface analysis. The 2D fingerprint plot analysis revealed that the H⋅⋅⋅H and H⋅⋅⋅Cl is found to be dominant contributors to the total Hirshfeld surface. The synthesized compound is optimized using B3LYP functional at 6–311+G(d,p) level of theory, the highest occupied and lowest unoccupied molecular orbitals are plotted for the optimized structure, further with various other electronic properties were evaluated. The docking studies revealed that the molecule might possess po- tential anti-cancer activity with a binding score of -8.1 kcal/mol against mitogen-activated protein kinases (MAPKs) when compared to the standard drug Fluorouracil. And further, based on the results of docking studies the CPIQ molecule was examined for its effect against the human colorectal cancer cells and human pancreatic ductal adenocarcinoma cells (PDAC) cells (HCT116, MIAPaCa2) with an effective IC50 of 12.35 and 19.77 μM respectively, to unveil its anticancer potential. And in addition, screened for drug likeness character of the molecule through online servers pkCSM and SwissADME, which suggest that the physicochemical and ADMET parameters are within an ideal range, the synthesized CPIQ molecule exhibits good pharmacokinetic properties.

Item Type:	Article
Uncontrolled Keywords:	Crystal structure, MAPK, Docking studies,ADMET, Anticancer
Subjects:	C Chemical Science > Chemistry
Divisions:	Department of > Chemistry
Depositing User:	Ms Varalakshmi
Date Deposited:	28 Oct 2025 09:50
Last Modified:	28 Oct 2025 09:50
URI:	http://eprints.uni-mysore.ac.in/id/eprint/17875

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