Current Trends in Pharmacy and Pharmaceutical Chemistry

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Gavande, Lavate, Dhakane, Jagtap, Kulkarni, and Varpe: Quinoline containing benzimidazole and their biological activities


Introduction

Quinoline and benzimidazole derivatives are known for their excellent potential for various pharmacological activities. Many marketed drugs contain these two heterocycles in their structures.

Figure 1

Structure of quinoline and bezimidazole

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Fluoroquinolone antibiotics, which have a fluorine atom in their molecular structure and are active against Gram-negative and Gram-positive bacteria, account for nearly all quinolone antibiotics currently in use.1 Ciprofloxacin, gemifloxacin, levofloxacin, moxifloxacin, and ofloxacin are fluoroquinolone antibiotics.2 Thiabendazole, flubendazole, astemizole, lansoprazole, and omeprazole are some of the commercially available benzimidazole-containing medications.3 There is an important place in drug discovery for quinolinyl and benzimidazole heterocycles. This review article focuses on quinolinyl and benzimidazole conjugates for their analgesic, anti-inflammatory, antibacterial, antifungal, antiviral, anti-parasitic, anti-Parkinson's disease, anticancer, antioxidants, antidiabetic, anticoagulant, and antimalarial activities. Most of the researchers have studied quinolinyl-based benzimidazole derivatives as models for the development of new antimicrobial agents.

The Quinoline ring system consists of heterocycles where a pyridine ring fuses the benzene ring. Quinoline derivatives have a range of biological activities such as antimicrobial4, anti-tuberculosis5, anti-inflammatory6, and anti-cancer.7 This review contains reported derivatives of quinoline and Benzimidazole and their biological activities.

Quinoline Benzimidazole Conjugates

El-Feky, S. A.et al.synthesized Benzimidazole and fluorinated quinoline derivatives and tested for anti-inflammatory activity and ulcerative effect. As they were an ulcerogenic activity, the most active compounds (1a-f) were found to be superior to celecoxib. Compound 1a showed the highest anti-inflammatory activity as well as the best binding profiles at the COX-2 binding site. It is stated that the existence of the acetamide linker in compounds 1a–f could favor activity over the non-substituted benzimidazole derivative.(Figure 1).6

Figure 2

Benzimidazole and fluorinated quinoline derivatives

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Brajša, K. et al. synthesized amidino-replaced benzimidazole and benzimidazo[1,2a] quinoline derivatives and studied them in 2D and 3D cell culture systems for their cytotoxic activities. Synthesized compounds were tested as a small platform to compare antitumor activity in 2D and 3D cell culture systems and comparison with the relationship between structure and function. A human cancer breast (SK-BR-3, MDA-MB-231, T47D) and pancreatic cancer cells (MIAPaCa2, PANC1) have been tested with the 3D cell culture method. Compounds have shown moderate to potent activities as compared to standards (Figure 3).7

Figure 3

Amidino-replaced benzimidazole and benzimidazo[1,2a] quinoline derivatives

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Garudachari, B. et al. synthesized Benzimidazole-quinoline derivatives and tested them for antimicrobial activities. The compounds weres screened using a well plate method (inhibition zone) for their antibacterial and antifungal activity invitro. There result showed strong antibacterial activity in compounds 3c, 3d, 3ac, and 3ad. It was found that the compound 3ab is a powerful antifungal agent. Compounds 3a, 3aa, and 3af showed Moderate to good antimicrobial activity.8

Figure 4

Benzimidazole-quinoline derivatives

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Mungra, D.C. et al synthesized benzimidazoles[1,5-a]quinoline-basedtetrazoloand tested for antimicrobial activity. Compound 4e showed significant activity against Bacillus subtilis Gram-positive bacteria. Compounds 4a and 4o were found significantly active against Bacillus subtilis compared with ampicillin (Figure 5).9

Figure 5

benzimidazoles[1,5-a]quinoline- derivatives

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Lamazzi, C. et al synthesized Cyanoindolo[3,2-c]quinolinesandBenzimidazo[1,2-c]quinazolinesand tested for cytotoxic activity. Compounds have shown excellent cytotoxic activity against murine L1210 leukemia cell line (Figure 6).10

Figure 6

Cyanoindolo[3,2-c]quinolinesandBenzimidazo[1,2-c]quinazolines

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Perin, N. et al synthesized 2-substitutedbenzimidazo[1,2-a]quinolines and tested for their antitumor activity. Compounds have shown activities in the range of 0.2 ->10 µM against HCT116, 2.5- 39 µM against MCF-7, and 0.2 ->10 µM against H460 (Figure 7).11

Figure 7

2-substitutedbenzimidazo[1,2-a]quinolines

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Ukrainets, I.V. et al. synthesized Benzimidazol-2-ylamidesof1-r-4-hydroxy2-oxo-1,2-dihydroquinoline-3-carboxylic acids are synthesized and tested for their antithyroid and antituberculosis activities. Compounds have shown moderate to potent antithyroid and antituberculosis activities.(Figure 8) 12

Figure 8

Benzimidazol-2-ylamidesof1-r-4-hydroxy2-oxo-1,2-dihydroquinoline-3-carboxylic acids

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Weinkauf. R. L. et al synthesized benzimidazo[1,2-b]-ouinoies,ndoo[2,3-]2quinoines, and pyridocarbazoles and tested for antineoplastic activity against HCT-116, 9-KB, and Topoisomerase II. Compounds have shown cytotoxicity against HCT-116 in the range of 0.8- >150 µ/mL, 9-KB in the range of 2.2- >150 µ/mL and 0.1-10 µ/mL (Figure 9).13

Figure 9

Benzimidazo[1,2-b]-ouinoies,ndoo[2,3-]2quinoines, and pyridocarbazoles

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Conclusion:

For their anti-cancer and antibacterial activities, quinoline and Benzimidazole derivatives are mostly studied. Various derivatives identified have demonstrated excellent biological activity. Synthesis and study of such designed molecules can lead to potent drug candidates being discovered.

Source of Funding

None.

Conflict of Interest

None.

References

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D C Mungra M P Patel R G Patel Microwave-assisted synthesis of some new tetrazolo[1,5-a]quinoline-based benzimidazoles catalyzed by p-TsOH and investigation of their antimicrobial activityMed Chem Res2011206782910.1007/s00044-010-9388-0

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C Lamazzi S Léonce B Pfeiffer P Renard G Guillaumet C W Rees Expeditious synthesis and cytotoxic activity of new cyanoindolo[3,2-c]quinolines and benzimidazo[1,2-c]quinazolinesBioorganic Med Chem Lett200010192183510.1016/s0960-894x(00)00427-3

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N Perin I M Kleiner R Nhili W Laine M H D Cordonnier O Vugrek Biological activity and DNA binding studies of 2-substituted benzimidazo[1,2-a]quinolines bearing different amino side chainsMedChemComm201341215375010.1039/c3md00193h

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I V Ukrainets L A Grinevich A A Tkach O V Gorokhova V N Kravchenko G Sim 4-hydroxy-2-quinolones. 191.* synthesis, tautomerism and biological activity of benzimidazol-2-ylamides of 1-r-4-hydroxy-2-oxo-1,2-dihydroquinoline-3-carboxylic acidsChem Heterocyclic Compounds2011461113647010.1007/s10593-011-0673-8

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R L Weinkauf A Y Chen C Yu L Liu L Barrows E J LaVoie Antineoplastic activity of benzimidazo[1,2-b]-isoquinolines, indolo[2,3-b]quinolines, and pyridocarbazolesBioorganic Med Chem199428781610.1016/s0968-0896(00)82177-x



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Article type

Review Article


Article page

3-6


Authors Details

Gajanan Gavande, Amol Lavate, Vaibhav Dhakane, Dnyaneshwar Jagtap, Amol Kulkarni, Bhushan D Varpe


Article History

Received : 26-05-2021

Accepted : 21-07-2021

Available online : 31-07-2021


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