Design, Synthesis, Antimicrobial Evaluation and Molecular Modeling Study of New 2-mercaptoimidazoles (Series-III)

Author(s): Nidhi Rani, Randhir Singh*.

Journal Name: Letters in Drug Design & Discovery

Volume 16 , Issue 5 , 2019

Submit Manuscript
Submit Proposal

Graphical Abstract:


Abstract:

Background: A series of novel substituted 2-mercaptoimidazoles was synthesised efficiently and in high yields using one-pot synthesis from m-hydroxyacetophenones.

Methods: The structures of the newly synthesized compounds were established, their molecular activity was investigated against some bacteria and fungi were further validated using molecular docking study.

Results: Reaction of o-hydroxyphenacylbromide (2) with substituted aniline and KSCN, in the presence of catalyst p-toluene sulfonic acid afforded 4(a-r) in good yield. The structure of compounds (4a-r) was confirmed by IR, NMR and MS.

Conclusion: The compounds exhibited excellent antimicrobial potency against the tested microorganism.

Keywords: Mercaptoimidazoles, imidazoles, molecular modeling, antifungal, antibacterial, m-hydroxyacetophenones.

[1]
Bellina, F.; Cauteruccio, S.; Rossi, R. Synthesis and biological activity of vicinal diaryl-substituted 1H-imidazoles. Tetrahedron, 2007, 63, 4571-4624.
[2]
Rani, N.; Sharma, A.; Singh, R. Imidazoles as promising scaffold for antibacterial activity: A review. Mini Rev. Med. Chem., 2013, 13, 1812-1835.
[3]
Rani, N.; Sharma, A.; Gupta, G.K.; Singh, R. Imidazoles as potential antifungal agents: A review. Mini Rev. Med. Chem., 2013, 13, 1626-1655.
[4]
Chen, J.; Wang, Z.; Lu, Y.; Dalton, J.T.; Millera, D.D.; Li, W. Synthesis and antiproliferative activity of imidazole and imidazoline analogues for melanoma. Bioorg. Med. Chem. Lett., 2008, 18, 3183-3187.
[5]
Dominianni, S.J.; Yen, T.T. Oral hypoglycemic agents. Discovery and structure-activity relationships of phenacylimidazolium halides. J. Med. Chem., 1989, 32, 2301-2306.
[6]
Nguyen, D.N.; Stump, C.A.; Walsh, E.S.; Fernandes, C.; Davide, J.P.; Ellis-Hutchings, M.; Robinson, R.G.; Williams, T.M.; Lobell, R.B.; Huber, H.E.; Buser, C.A. Potent inhibitors of farnesyltransferase and geranylgeranyltransferase-I. Bioorg. Med. Chem. Lett., 2002, 12, 1269-1273.
[7]
Mano, T.; Stevens, R.W.; Ando, K.; Nakao, K.; Okumura, Y.; Sakakibara, M.; Okumura, T.; Tamura, T.; Miyamoto, K. Novel imidazole compounds as a new series of potent, orally active inhibitors of 5-lipoxygenase. Bioorg. Med. Chem., 2003, 11, 3879-3887.
[8]
Jackson, P.F.; Bullington, J.L. Pyridinylimidazole based p38 MAP kinase inhibitors. Curr. Top. Med. Chem., 2002, 2, 1011-1020.
[9]
Bolos, J. Structure-activity relationships of p38 mitogen-activated protein kinase inhibitors. Mini Rev. Med. Chem., 2005, 5, 857-868.
[10]
Dyck, B.; Goodfellow, V.S.; Phillips, T.; Grey, J.; Haddach, M.; Rowbottom, M.; Naeve, G.S.; Brown, B.; Saunders, J. Potent imidazole and triazole CB1 receptor antagonists related to SR141716. Bioorg. Med. Chem. Lett., 2004, 14, 1151-1154.
[11]
Lange, J.H.M.; Neut, M.A.W. Wals; H.C., Kuil, G.D.; Borst, A.J.M.; Mulder, A.; Hartog, A.P.; Zilaout, H.; Goutier, W.; Stuivenberg, H.H.; Vliet, B.J. Synthesis and SAR of novel imidazoles as potent and selective cannabinoid CB2 receptor antagonists with high binding efficiencies. Bioorg. Med. Chem. Lett., 2010, 20, 1084-1089.
[12]
Kiselyov, A.S.; Semenova, M.; Semenov, V.V. Hetarylimidazoles: A novel dual inhibitors of VEGF receptors I and II. Bioorg. Med. Chem. Lett., 2006, 16, 1440-1444.
[13]
Blum, C.A.; Zheng, X.; De Lombaert, S. Design, synthesis, and biological evaluation of substituted 2-cyclohexyl-4-phenyl-1H-imidazoles: Potent and selective neuropeptide Y5-receptor antagonists. J. Med. Chem., 2004, 47, 2318-2325.
[14]
Rani, N. Synthesis, biological evaluation and computational study of some new imidazole derivatives. M. Pharma Dissertation, Maharishi Markandeshwar University, Mullana. June . 2011.
[15]
Gupta, G.K.; Rani, N.; Kumar, V. Microwave assisted synthesis of imidazoles-A review. Mini Rev. Org. Chem., 2012, 9, 270-284.
[16]
Rani, N.; Gupta, G.K.; Kumar, V.; Kumar, V. Imidazole: A potential scaffold for antimicrobial activity. Global J. Pharma. Edu. Res, 2012, 1, 7-16.
[17]
a)Rani, N.; Sharma, A.; Singh, R. Trisubstituted imidazole synthesis: A review. Min Rev. Org. Chem., 2015, 12(1), 34-65.
b)Rani, N.; Kumar, P.; Singh, R.; Sharma, A. Molecular docking evaluation of imidazole analogues as potent C. albicans14α-demethylase inhibitors. Curr. Comp. Aided Drug des, 2015, 11(4), 8-20.
[18]
Vogel, A.I. A text-book of Practical organic Chemistry; Third edition, by longmann Group Limited, London, 962, 1956.
[19]
Rani, N.; Singh, R. Molecular modeling Investigation of some new 2-mercaptoimidazoles. Curr. Comp. Aided Drug Design, 2017, 13, 1.
[20]
Aggarwal, R.; Kumar, R.; Kumar, V. A facile and rapid one-pot synthesis of 1,4-diaryl-2-mercaptoimidazoles under solvent-free conditions. J. Sulfur Chem., 2007, 28, 617-623.
[21]
Sadashiva, M.P.; Mallesha, H.; Hitesh, N.A.; Rangappaa, K.S. Synthesis and microbial inhibition study of novel 5-imidazolyl substituted isoxazolidines. Bioorg. Med. Chem., 2004, 12, 6389-6395.
[22]
Rossello, A.; Bertini, S.; Lapucci, A.; Macchia, M.; Martinelli, A.; Rapposelli, S.; Herreros, E.; Macchia, B. Synthesis, antifungal activity, and molecular modeling studies of new inverted oxime ethers of Oxiconazole. J. Med. Chem., 2002, 45, 4903-4912.
[23]
Thomsen, R.; Christensen, M.H. MolDock: A new technique for high-accuracy molecular docking. J. Med. Chem., 2006, 49, 3315-3321.


Rights & PermissionsPrintExport Cite as


Article Details

VOLUME: 16
ISSUE: 5
Year: 2019
Page: [512 - 521]
Pages: 10
DOI: 10.2174/1570180815666181015144431
Price: $58

Article Metrics

PDF: 13
HTML: 2
EPUB: 1
PRC: 1