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.

Diversity-oriented synthesis of 1H-1,2,3-triazole tethered pyrazolo[5,1-b]quinazoline hybrids as antimicrobial agents.

A straightforward and high yielding synthetic approach is employed to synthesize the novel 1H-1,2,3-triazole tethered pyrazolo[5,1-b]quinazoline hybrids 7(a-t) as new antimicrobial agents with two pharmacophore in the effective two step synthesis. The first step is the four component one-pot synthesis of highly functionalized pyrazolo[5,1-b]quinazolines 5(a-j) catalysed by TBAB, with the advantages of an environmentally benign reaction, high yielding, quick reaction time, and operational simplicity. In the subsequent stage, CuSO4/NaAsc system was employed to synthesize the 1H-1,2,3-triazole tethered pyrazolo[1,5-b]quinazoline hybrids as 1H-1,2,3-triazoles are the structures of great diversity and importance in diverse therapeutics containing numerous biological activities. The antimicrobial activity of all the synthesized hybrid compounds have been preliminary tested using the broth dilution technique against two gram-positive and two gram-negative bacterial strains as well as two fungal strains. In comparison to standard drugs, the majority of compounds exhibited good to moderate activity. Among the all the compounds, 7a (MIC 18.54 µM) against Pseudomonas aeruginosa, 7j (MIC 89.76 µM) against Bacillus subtilis as well as Rhizopus oryzae and 7t (MIC 84.88 µM) against Aspergillus parasiticus have remarkable antimicrobial potency as compared to standard drug.

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).

Meglumine-based Sustainable Three-component Deep Eutectic Solvent Applicable for the Synthesis of Pyrazolo[5,1-b]quinazoline-3-carboxylates as a Sensing Probe for Cu2+ Ions.

An unprecedented meglumine-based three-component deep eutectic solvent (3c-DES) (MegPAc) was synthesized using meglumine, p-toluenesulfonic acid (PTSA), and acetic acid as a renewable, and non-toxic solvent. The exploitation of the MegPAc as an eco-friendly reaction media to construct a selective and sensitive small organic molecular sensing probe, namely, pyrazolo[5,1-b]quinazoline-3-carboxylates (PQCs) was executed. Captivatingly, the MegPAc served the dual role of solvent and catalyst, and it delivered the title components with 69-94 % yields within 67-150 minutes. Furthermore, a UV-visible study unfolds the selective detection of Cu2+ ions with our synthetic probe 4 ba and resulted in hypsochromic shift due to electrostatic interactions. Additionally, 1H NMR titration study and density functional theory (DFT) calculations were performed to attest the binding mechanism of sensing probe 4 ba and Cu2+ ions. Worthy of mention, this protocol unveils the efficacy of meglumine-based 3c-DES for the first time as a bio-renewable system to synthesize the PQCs.

In silico and in vitro evaluation of newly synthesized pyrazolo-pyridine fused tetrazolo-pyrimidines derivatives as potential anticancer and antimicrobial agents.

Diversely functionalized pyrazolo-pyridine fused tetrazolo-pyrimidines 10aa-am and 10ba-bn were successfully synthesized via a catalyst-free synthetic protocol with moderate to very good yields. The compounds were evaluated for cytotoxicity against MCF-7 and HEK-293 cells using MTT assay. Among the tested compounds, 10ab (IC50- 23.83 µM) and 10ah (IC50- 23.30 µM) demonstrated the highest potency against MCF-7 cells, while 10bc (IC50- 14.46 µM) and 10bh (IC50- 2.53 µM) exhibited excellent cytotoxicity against HEK-293 cells. Additionally, antibacterial screening was performed against three Gram-negative bacteria (E. coli, P. aeruginosa, and S. enterica) and three Gram-positive bacteria (S. aureus, B. megaterium, and B. subtilis) using broth dilution method, while antifungal activity was assessed against three fungal strains (A. niger, Penicillium, and S. cerevisiae) using agar well diffusion method. In antimicrobial screening, the majority of the compounds demonstrated significant antibacterial efficacy compared to antifungal activity. We also conducted comprehensive computational studies, including DFT calculations, molecular docking and dynamics, and drug-likeness assessments. In the DFT study, compounds 10ac and 10bc displayed stable conformations, indicating their potential for higher therapeutic activity. Molecular docking analyses revealed compelling interactions, with compound 10ah demonstrating docking score -7.42 kcal/mol against catalytical domain PARP1 (PDB ID: 7KK4) and 10bh exhibiting a best docking score -10.77 kcal/mol against human corticotropin-releasing factor receptor 1 (PDB ID: 4Z9G). A 100 ns molecular dynamics (MD) simulation study of compounds 10ah and 10bh revealed the stable conformation and binding energy in a stimulating environment. In drug-likeness assessments, both the compounds 10ah and 10bh adhere all the established guidelines.Communicated by Ramaswamy H. Sarma.

Meglumine-Promoted Eco-Compatible Pseudo-Three-Component Reaction for the Synthesis of 1,1-Dihomoarylmethane Scaffolds and Their Green Credentials.

A simple, straightforward, and energy-efficient greener route for the synthesis of a series of biologically interesting functionalized 1,1-dihomoarylmethane scaffolds has been developed in the presence of meglumine as an efficient and eco-friendly organo-catalyst via one-pot pseudo-three-component reaction at room temperature. Following this protocol, it is possible to synthesize 1,1-dihomoarylmethane scaffolds of an assortment of C-H activated acids such as dimedone, 1,3-cyclohexadione, 4-hydroxy-6-methyl-2-pyrone, 4-hydroxycoumarin, and 1-phenyl-3-methyl-pyrazolone. The salient features of the present green protocol are mild reaction conditions, good to excellent yields, operational simplicity, easy isolation of products, no cumbersome post treatment, high atom economy, and low E-factor. In addition, this chemistry portrays several green advantages including the reusability of reaction media and product scalability, which makes protocol sustainably efficient. Additionally, several control experiments such as protection of catalyst reactive site, D2O exchange, and 1H NMR studies revealed possible pathways for meglumine-promoted reactions. Inspired by the natural physiological environment of 1,1-dihomoarylmethane scaffolds, we reconnoitered the biological profile of our compounds and synthesized compounds that were promising for their antiproliferative and antibacterial activities.