Microwave-induced one-pot synthesis of 3-imidazolyl indole clubbed 1,2,3-triazole hybrids as antiproliferative agents and density functional theory study.

Herein, we outline a highly efficient PEG-4000-mediated one-pot three-component reaction for the synthesis of 3-imidazolyl indole clubbed 1,2,3-triazole derivatives (5a-r) at up to 96% yield as antiproliferative agents. This three-component protocol offers the advantages of an environmentally benign reaction, excellent yield, quick response time, and operational simplicity triggered by the copper catalyst under microwave irradiation. All the synthesized compounds were tested for antiproliferative activity against six human solid tumor cell lines, that is, A549 and SW1573 (nonsmall cell lung), HBL100 and T-47D (breast), HeLa (cervix), and WiDr (colon). Among them, six compounds, 5g-j, 5m, and 5p, demonstrated effective antiproliferative action with GI50 values under 10 µM. Furthermore, density functional theory (DFT) calculations were performed for all the synthesized molecules through geometry optimizations, frontier molecular orbital approach, and molecular electrostatic potential (MESP). The theoretical DFT calculation was performed using the DFT/B3LYP/6-31+G (d,p) basis set. Moreover, the biological reactivity of all the representative synthesized molecules was compared with the theoretically calculated quantum chemical descriptors and MESP 3D plots. We also investigated the drug-likeness characteristic and absorption, distribution, metabolism, excretion, and toxicity (ADMET) prediction. In general, our approach enables environmentally friendly access to 3-imidazolyl indole clubbed 1,2,3-triazole derivatives as prospective antiproliferative agents.

Ultrasound-promoted convenient and ionic liquid [BMIM]BF4 assisted green synthesis of diversely functionalized pyrazolo quinoline core via one-pot multicomponent reaction, DFT study and pharmacological evaluation.

An ultrasound-assisted green protocol for one-pot synthesis of a new series of pharmaceutically relevant pyrazolo quinoline derivatives (4a-t) were synthesized, characterized, and evaluated using DFT and biological activities. Pyrazolo quinoline derivatives (4a-t) were synthesized via a three-component tandem reaction of 1,3-dicarbonyl compound (1a-b), substituted aromatic aldehyde (2a-o), and 5-amino indazole (3a) in the presence of 1-butyl-3-methylimidazolium tetrafluoroborate [BMIM]BF4 ionic liquid in ethanol at ambient conditions. The main purpose of the present work is selective functionalization of pyrazolo quinoline (4a-t) core excluding another potential parallel reaction under environmentally benign reaction conditions. The present protocol shows features such as amphiphilic behavior of ionic liquid during reaction transformation, and reusability of the [BMIM]BF4 ionic liquid under mild reaction condition. All newly derived compounds were evaluated for their in vitro anti-inflammatory and antioxidant activity. Among them, compound 4c showed encouraging antioxidant activity compared with standard antioxidant ascorbic acid, and compounds 4n and 4r displayed very good anti-inflammatory activity compared with a standard drug. In this study, a theoretical computational density functional study was also executed to perform the geometry optimizations, frontier molecular orbital approach, and molecular electrostatic potential (MESP). The DFT study was carried out with the basis set DFT/B3LYP/6-31+G (d, p) level of theory. The quantum chemical descriptors (QCDS) and MESP diagrams were plotted to examine the biological reactivities of representative pyrazolo quinolines (4a-t).