Green Synthesis of Oxoquinoline-1(2H)-Carboxamide as Antiproliferative and Antioxidant Agents: An Experimental and In-Silico Approach to High Altitude Related Disorders.

Amena Ali,Mohamed Jawed Ahsan,Faizul Azam,Abuzer Ali,Musarrat Husain Warsi,Mohammad Akhlaquer Rahman

doi:10.3390/molecules27010309

Amena Ali, Mohamed Jawed Ahsan + Show 4 more

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https://doi.org/10.3390/molecules27010309

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Abstract

At high altitudes, drops in oxygen concentration result in the creation of reactive oxygen and nitrogen species (RONS), which cause a variety of health concerns. We addressed these health concerns and reported the synthesis, characterization, and biological activities of a series of 10 oxoquinolines. N-Aryl-7-hydroxy-4-methyl-2-oxoquinoline-1(2H)carboxamides (5a–j) were accessed in two steps under ultrasonicated irradiation, as per the reported method. The anticancer activity was tested at 10 µM against a total of 5 dozen cancer cell lines obtained from nine distinct panels, as per the National Cancer Institute (NCI US) protocol. The compounds 5a (TK-10 (renal cancer); %GI = 82.90) and 5j (CCRF-CEM (Leukemia); %GI = 58.61) showed the most promising anticancer activity. Compound 5a also demonstrated promising DPPH free radical scavenging activity with an IC50 value of 14.16 ± 0.42 µM. The epidermal growth factor receptor (EGFR) and carbonic anhydrase (CA), two prospective cancer inhibitor targets, were used in the molecular docking studies. Molecular docking studies of ligand 5a (docking score = −8.839) against the active site of EGFR revealed two H-bond interactions with the residues Asp855 and Thr854, whereas ligand 5a (docking = −5.337) interacted with three H-bond with the residues Gln92, Gln67, and Thr200 against the active site CA. The reported compounds exhibited significant anticancer and antioxidant activities, as well as displayed significant inhibition against cancer targets, EGFR and CA, in the molecular docking studies. The current discovery may aid in the development of novel compounds for the treatment of cancer and oxidative stress, and other high altitude-related disorders.

Highlights

At high altitude, the concentration of oxygen decreases, resulting in the formation of reactive oxygen and nitrogen species (RONS) [1]
An equimolar mixture of 7-hydroxy-4-methyl-2H-chromen-2-one (3) (1 mmol; 176 mg) and substituted phenyl urea (4a–j) (1 mmol) in 10 mL water was ultrasonicated for 20–25 min (20 KHz; 130 W) and the final precipitate was separated by vacuum filtration followed by washing with water and re-crystallized from absolute ethanol to obtain the target title compounds (5a–j)
We investigated and compared the scope of this synthetic method under optimize conditions in both at the elevated temperature (200 ◦C) in solvent free conditions, as well as under ultrasonicated modes in water as a green solvent

Summary

Introduction

The concentration of oxygen decreases, resulting in the formation of reactive oxygen and nitrogen species (RONS) [1]. High altitude RONS production causes lipid, protein, and DNA damage, as well as weakening of the enzymatic and non-enzymatic antioxidant systems [2]. Several ailments, including cancer, Alzheimer’s, and diabetes, as well as motion sickness, may occur as a result of high-altitude oxidative stress [8,9]. Apoptosis, cell growth and survival, nucleic acid synthesis, and oxidative stress are all controlled by mitochondrial signaling. Mitochondrial malfunction and the resulting mishandling of the reactive oxygen species (ROS) cascade have been linked to cancer progression [10,11]. Oxidative stress can potentially cause malignant cell growth [13]

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