Evaluation of Spirooxindole-3,3'-pyrrolines-incorporating Isoquinoline Motif as Antitumor, Anti-inflammatory, Antibacterial, Antifungal, and Antioxidant Agents
Authors: Jaber Areej M. , Zahra Jalal A. , El-Abadelah Mustafa M. , Al-Mahadeen Mohammed M. , Sabri Salim S. , Kasabri Violet , Haddadin Randa N. 
Published: July 2024

Background:

A series of novel 2-(isoquinolin-1-yl)-spiro[oxindole-3,3′-pyrrolines] were synthesized by a one-pot three-component reaction involving dimethyl acetylenedicar-boxylate, 3-phenylimidazo[5,1-a]isoquinoline and N-alkylisatins in chloroform at ∼60°C for 24 h.

Aims:

This study aimed at the synthesis of novel spirooxindole-3,3'-pyrrolines derivatives and in vitro evaluation of cytotoxicity affinities in cross-correlations with their anti-inflammation and radical scavenging capacities.

Objectives:

The objective of this study was to use a one-pot, three-component reaction to syn-thesize a novel set of spirooxindole-3,3'-pyrrolines derivatives.

Methods:

A novel set of spirooxindole-3,3'-pyrrolines (8a-i) was synthesized by a one-pot three-component reaction involving dimethyl acetylenedicarboxylate, 3-phenylimidazo[5,1-a]isoquinoline and N-alkylisatins in chloroform at ∼60°C for 24 h. These new compounds were characterized by 1HNMR, 13C-NMR, and HRMS spectral data and screened for their antitumor, anti-inflammatory, antibacterial, antifungal, and antioxidant activities.

Results:

The new synthetic spirooxindole-3,3'-pyrrolines (8a-i)-tested compounds displayed significant anti-inflammatory properties and were noncytotoxic on PDL fibroblasts. However, they lacked antioxidative-DPPH radical scavenging capabilities. Notably, Doxorubicin and cisplatin demonstrated antiproliferative effects on various cancer monolayers. Moreover, com-pounds 8b, 8d, 8f, 8h, and 8i exhibited pronounced viability reduction properties in colorectal and pancreatic cancer monolayers, as well as across skin, lung, prostate, and cervical adeno-carcinomas, with higher cytotoxicity in mammary cancer cells MCF7 and T47D. None of the tested compounds had significant antibacterial activity against S. aureus or E. coli. However, compounds 8c, 8d, and 8f exhibited notable antifungal properties, indicating potential for fur-ther investigation.

Results:

The new synthetic spirooxindole-3,3'-pyrrolines (8a-i)-tested compounds displayed significant
anti-inflammatory properties and were noncytotoxic on PDL fibroblasts. However, they lacked
antioxidative-DPPH radical scavenging capabilities. Notably, Doxorubicin and cisplatin demonstrated
antiproliferative effects on various cancer monolayers. Moreover, compounds 8b, 8d, 8f, 8h,
and 8i exhibited pronounced viability reduction properties in colorectal and pancreatic cancer monolayers,
as well as across skin, lung, prostate, and cervical adenocarcinomas, with higher cytotoxicity
in mammary cancer cells MCF7 and T47D. None of the tested compounds had significant antibacterial
activity against S. aureus or E. coli. However, compounds 8c, 8d, and 8f exhibited notable
antifungal properties, indicating potential for further investigation.

Conclusion:

Eight new synthetic spiro[indoline-3,3-pyrroles] were prepared, characterized, and evaluated for their anti-inflammatory and cytotoxic properties. The compounds showed significant anti-inflammatory effects and promising cytotoxicity against various cancer mon-olayers, especially in colorectal and pancreatic cancers. Some compounds also exhibited anti-fungal properties. However, they did not exhibit significant antibacterial activity.