Synthesis of Dihydrobenzimidazoquinazoline Derivatives for Their Potential Biological Activities
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1
Department of Chemistry, Faculty of Science, Putra Malaysia University, Malaysia
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2
Integrated Chemical BioPhysics Research, Faculty of Science, Universiti Putra Malaysia,, Maldives
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3
Integrated Chemical BioPhysics Research, Faculty of Science, Universiti Putra Malaysia, Malaysia
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4
Laboratory of Natural Product, Institute of Bioscience, University Putra Malaysia, Malaysia
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5
College of Pharmacy, Al-Mustansiriya University, Iraq
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6
Laboratory of Molecular Biomedicine, Institute of Bioscience, University Putra Malaysia, Malaysia
Background
Heterocyclic compounds, whether natural or synthetic, are known for their vast biological activities and therapeutic potentials. Quinazoline and benzimidazoles derivatives have exhibited anti-tumour, anti-microbial, anti-viral, anti-tuberculosis and anti-inflammatory activities in separate occasion. Herein the synthesis of a series of dihydrobenzimidazoquinazoline derivatives was carried out as it was postulated that combination of these two heterocyclic moieties would exhibit excellent biological activities. Antioxidant activities of the compounds were screened as a low cost, predictive tool for their actual biological activities such as anticancer activity. The antibacterial and antifungal activities of the compounds were also evaluated.
Methods
Using microwave and conventional heating method, a series of dihydrobenzimidazoquinazoline derivatives (compound 1-7) was produced via condensation of 2-(2-aminophenyl)-1H-benzimidazole with a series of aliphatic aldehydes [propanal (1), butanal (2), isobutyraldehyde (3), hexanal (4), octanal (5), hydrocinnamaldehyde (6) and cinnamaldehyde (7)]. The anti-oxidant activities of the compounds were screened using two different methods: DPPH and ABTS scavenging activities. The antimicrobial activities of the compounds against four pathogenic bacteria (Staphyloccus aureus, Bacillus subtilis, Pseudomonas aeruginosa, Salmonella choleraesuis) and one fungus (Aspergillus brasilliensis) were determined. Tetracycline (antibacterial) and nystatin (antifungal) were used as the positive control.
Results
Seven (5 new) dihydrobenzimidazoquinazoline compounds were successfully synthesized and characterized. Both methods, microwave and conventional heating produced the compounds in excellent yield but the microwave method was far superior in term of the time needed to complete the reaction, only 5 mins compared to conventional heating (35 – 80 mins). All compounds showed moderate DPPH scavenging activities (13.95 - 24.54 mg/TE.g-1). Interestingly, the compounds exhibited excellent and better ABTS scavenging activities (382.70 – 774.2 mg/TE.g-1) and compound 1 with the smallest alkyl side chain (ethyl group) showed the best activities in both antioxidant tests. Compounds 1, 2 and 4 showed moderate activity against the Gram positive Staphyloccus aureus but only poor activity against Bacillus subtilis. All compounds showed no activity against the Gram negative bacteria (Pseudomonas aeruginosa, Salmonella choleraesuis) and the fungus (Aspergillus brasilliensis). Compounds bearing straight alkyl side chain showed better antibacterial activity than compounds having branch or aromatic side chain.
Conclusion
Synthesis of dihydrobenzimidazoquinazoline compounds was successful using both microwave and conventional heating. All compounds exhibited good antioxidant activity. Some compounds showed selective activity against Gram positive bacteria.
Acknowledgements
We would like to acknowledge College of Pharmacy, Al-Mustansiriyah University, Baghdad, Iraq for HAH scholarship and Universiti Putra Malaysia for grant GP-IPS/2016/0474300.
Keywords:
dihydrobenzimidazoquinazoline,
antioxidant,
antimicrobial,
Heterocyclic,
Microwave
Conference:
International Conference on Drug Discovery and Translational Medicine 2018 (ICDDTM '18)
“Seizing Opportunities and Addressing Challenges of Precision Medicine”, Putrajaya, Malaysia, 3 Dec - 5 Feb, 2019.
Presentation Type:
Oral Presentation
Topic:
Miscellaneous
Citation:
Abdulmalek
E,
Abdul Rahman
M,
Shaari
K,
Hasan
HA and
Chan
KW
(2019). Synthesis of Dihydrobenzimidazoquinazoline Derivatives for Their Potential Biological Activities.
Front. Pharmacol.
Conference Abstract:
International Conference on Drug Discovery and Translational Medicine 2018 (ICDDTM '18)
“Seizing Opportunities and Addressing Challenges of Precision Medicine”.
doi: 10.3389/conf.fphar.2018.63.00041
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Received:
22 Oct 2018;
Published Online:
17 Jan 2019.
*
Correspondence:
Dr. Emilia Abdulmalek, Department of Chemistry, Faculty of Science, Putra Malaysia University, Serdang, Malaysia, emilia@upm.edu.my