Synthetic Methods of Quinoline Derivatives as Potent Anticancer Agents

Quinoline and benzofuran moieties are commonly used for the synthesis of therapeutically beneficial molecules and drugs since they possess a wide range of pharmacological activities including potent anticancer activity as compared to other heterocyclic compounds. Many of well-known antimalarial, antimicrobial, anti-helminthic, analgesic, anti-inflammatory, antiprotozoal, and antitumor compounds contain quinoline/benzofuran skeleton. The aim of this study was to analyze ten new quinoline and eighteen benzofuran derivatives for carcinoma cell line growth inhibition and to predict possible interactions with the target. The anticancer activity of these compounds against colon cancer (HCT-116) and triple-negative breast cancer (MDA-MB-468) cell lines was determined and performed molecular docking to predict the possible interactions. Among ten quinoline derivatives, Q1, Q4, Q6, Q9, and Q10 were found to be the most potent against HCT-116 and MDA-MB-468 with IC50 values ranging from 6.2-99.6 and 2.7-23.6 μM, respectively. Using the IC50 values, a model equation with quantitative structure activity relationship (QSAR) was generated with their descriptors such as HBA1, HBA2, kappa (1, 2 and 3), Balaban index, Wiener index, number of rotatable bonds, log S, log P and total polar surface area (TPSA). The effect of benzofuran derivatives was moderate in cytotoxicity tests and hence only quinolines were considered for further analysis. The molecular docking indicated the mammalian / mechanistic target of rapamycin (mTOR), Topoisomerase I and II as possible targets for these molecules. The predicted results obtained from QSAR and molecular docking analysis of quinoline derivatives showed high correlation in comparison to the results of the cytotoxic assay. Overall, this study indicated that quinolines are more potent as anticancer agents compared to benzofurans. Further, compound Q9 has emerged as a lead molecule which could be the base for further development of more potent anticancer agents.

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Design, Synthesis, and In Vitro Evaluation of Novel Indolyl DiHydropyrazole Derivatives as Potential Anticancer Agents

Molecules ◽

10.3390/molecules26175235 ◽

2021 ◽

Vol 26 (17) ◽

pp. 5235

Author(s):

Katharigatta N. Venugopala ◽

Mohammed Habeebuddin ◽

Bandar E. Aldhubiab ◽

Afzal Haq Asif

Keyword(s):

Anticancer Activity ◽

Cell Lines ◽

Anticancer Agents ◽

Human Cancer ◽

Structural Features ◽

Synthetic Methods ◽

Potential Candidate ◽

Human Cancer Cell Lines ◽

Hybrid Molecules

Indoles derived from both natural sources or artificial synthetic methods have been known to interact with aryl hydrocarbon receptors (AhR), and exhibit anticancer activity. In light of these attractive properties, a series of hybrid molecules with structural features of indoles, i.e., those bearing a pyrazoline nucleus, were evaluated for their enhanced anticancer activity. The designed molecules were subjected to molecular docking in order to screen for potential AhR interacting compounds, and the identified indolyl dihydropyrazole derivatives were synthesized. The synthesized compounds were characterized, and their cytotoxicity was evaluated against four human cancer cell lines using the MTT assay. Based on the Glide g-score, H-bonding interactions and bonding energy of 20 candidate molecules were selected for further analysis from the 64 initially designed molecules. These candidate molecules have shown promising anti-proliferative activity against the cell lines tested. Among these candidate molecules, the compounds with hydroxy phenyl substitution on the pyrazoline ring have shown potent activity across all the tested cell lines. The designed scaffold was proven effective for screening potential candidate molecules with anticancer properties, and may be further optimized structurally for yielding the ideal anti-tumorigenic compound for the treatment of various cancers.

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Fused pyrrolo-pyridines and pyrrolo-(iso)quinoline as anticancer agents

Physical Sciences Reviews ◽

10.1515/psr-2021-0030 ◽

2022 ◽

Vol 0 (0) ◽

Author(s):

Dorina Amariucai-Mantu ◽

Vasilichia Antoci ◽

Monica Cornelia Sardaru ◽

Cristina Maria Al Matarneh ◽

Ionel Mangalagiu ◽

...

Keyword(s):

Anticancer Agents ◽

Quinoline Derivatives

Abstract This work emphasizes the synthesis strategies and antiproliferative related properties of fused pyrrolo-pyridine (including indolizine and azaindoles) and pyrrolo-(iso)quinoline derivatives recently reported in literature.

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Synthetic Approaches of Pyrazolyl Quinolines

Mini-Reviews in Organic Chemistry ◽

10.2174/1570193x15666180419142511 ◽

2019 ◽

Vol 16 (4) ◽

pp. 353-360 ◽

Cited By ~ 1

Author(s):

Rizk E. Khidre ◽

Ibrahim Ali M. Radini ◽

Diaa A. Ibrahim

Keyword(s):

Glucose Transport ◽

Pyrazole Ring ◽

Review Article ◽

Synthetic Methods ◽

Medical Applications ◽

Quinoline Derivatives ◽

Quinoline Ring ◽

Transport Inhibitors ◽

Anti Inflammatory ◽

Synthetic Approaches

This review article represents a survey of the synthetic strategies leading to pyrazolyl quinolines. The synthetic methods are divided into two main groups based on the type of starting reagents: 1) From quinoline ring onto a pyrazole scaffold, 2) From pyrazole ring onto a quinoline scaffold. Also, some medical applications of pyrazolyl quinoline derivatives are mentioned such as anticancer, cell proliferative disorder, glucose transport inhibitors, anti-inflammatory, and inhibitors of leukotriene production for the treatment of cardiovascular. The main purpose of this review is to present a survey of the literature on the synthetic approaches of pyrazolyl quinolines and provide useful and up-to-date data for organic and medicinal chemist since such compound has not been previously reviewed.

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