Author(s):
Suresh Kumar, Renu Saharan, Randhir Singh
Email(s):
sureshmpharma@rediffmail.com
DOI:
10.52711/0974-360X.2021.00542 
Address:
Suresh Kumar1*, Renu Saharan2, Randhir Singh2
1Department of Pharmaceutical Chemistry, P.M. College of Pharmacy, Kami, Sonipat (Haryana), India.
2Maharishi Markandeshwar Deemed to be University, Mullana, Ambala (Haryana), India.
*Corresponding Author
Published In:
Volume - 14,
Issue - 6,
Year - 2021
ABSTRACT:
The synthesis of biologically active molecules carried out by using Aminothiazole nuclei and their various derivatives as precursors. In present work, Schiff's bases (27-36) were prepared by reacting amino group of thiazole moiety (26) with various aromatic aldehydes. The titled, novel 2-substituted aminothiazoles (37-46) were obtained by reaction of these Schiff's bases with benzil by providing excess amount of ammonium acetate (NH4OAc). Structure elucidation of all the newly synthesized compounds was carried out by employing elemental analysis, FT-IR, 1H NMR and Mass spectrometry. The newly synthesized novel 2-substituted-aminothiazoles were screened for their anti-bacterial activity against two gram +ve bacterial strains viz. Staphylococcus aureus and Bacillus subtilis and against a gram –ve bacterial strain viz. Escherichia coli and for anti-fungal activity against two fungal strains viz. Candida albicans and Aspergillus niger using cup plate method by using Norfloxacin and Fluconazole as standard drugs respectively. Cyto-toxic activity of the synthesized compounds was evaluated by determining the percentage growth inhibition of Dalton?s Lymphoma Ascites (DLA) cells and Erlich?s Ascites Carcinoma (EAC) cells by Tryphan Blue Dye Exclusion technique. Results of biological activity studies indicated that the newly synthesized 2-substituted aminothiazoles displayed good anti-bacterial activity against gram –ve bacterial strain Escherichia coli and anti-fungal activity against Candida albicans. Further, these compounds were found to show significant percent growth inhibition against DLA and EAC, cell-lines.
Cite this article:
Suresh Kumar, Renu Saharan, Randhir Singh. Synthesis, Characterization and Biological Evaluation of some Novel 2-Substituted Aminothiazoles. Research Journal of Pharmacy and Technology. 2021; 14(6):3104-0. doi: 10.52711/0974-360X.2021.00542
Cite(Electronic):
Suresh Kumar, Renu Saharan, Randhir Singh. Synthesis, Characterization and Biological Evaluation of some Novel 2-Substituted Aminothiazoles. Research Journal of Pharmacy and Technology. 2021; 14(6):3104-0. doi: 10.52711/0974-360X.2021.00542 Available on: https://www.rjptonline.org/AbstractView.aspx?PID=2021-14-6-32
REFERENCES:
1. Nevagi, R. J. Biological and medicinal significance of 2-aminothiazoles. Der Pharmacia Lettre. 2014; 6 (5): 134-150.
2. Kesicki, E. A.; Bailey, M. A.; Ovechkina, Y.; Early, J. V.; Bowman, T. A. J.; Zuniga, E. S.; Dalai, S.; Kumar, N.; Masquelin, T.; Hipskind, P. A.; Odingo, J. O.; Parish, T. Synthesis and Evaluation of the 2-Aminothiazoles as Anti-Tubercular Agents. Plos One. 2016; 1-25.
3. Al-Said, M. S.; Bashandy, M. S.; Al-Qasoumi, S. I.; Ghorab, M. M. Anti-breast cancer activity of some novel 1, 2-dihydropyridine, thiophene and thiazole derivatives. Eur J Med Chem. 2011; 46: 137-141.
4. Chimenti, F.; Bizzarri, B.; Bolasco, A.; Secci, D.; Chimenti, P. Synthesis and biological evaluation of novel 2, 4-disubstituted-1, 3-thiazoles as anti-Candida spp. agents. Eur. J. Med. Chem. 2011; 46: 378-382.
5. Yamaguchi, K.; Hori, F.; Hasegawa, S.; Nakashima, N.; Furukawa, H.; Hayano, T.; Takegoshi, K.; Murai, T. 5-Aminothiazoles: New Fluorescent Molecules Showing Multichromism. Second Interdisciplinary and Research Alumni Symposium iJaDe 2018.
6. Das, D.; Sikdar, P.; Bairagi, M. Recent developments of 2-aminothiazoles in medicinal chemistry. Eur. J. Med. Chem. 2016; 109: 89-98.
7. Dahiya, R.; Singh, S. First Total Synthesis and Biological Potential of Heptacyclopeptide of Plant Origin. Chin. J. Chem. 2016; 34: 1158-1164.
8. Dahiya, R.; Singh, S.; Sharma, A.; Chennupati, S.V.; Maharaj, S. First Total Synthesis and Biological Screening of a Proline-Rich Cyclopeptide from a Caribbean Marine Sponge. Marine Drugs. 2016; 14 (228): 1-14.
9. Dahiya, R.; Singh, S. Toward the Synthesis and Pharmacological Screening of a Natural Cycloheptapeptide of Plant Origin. Nat. Pro. Comm. 2017; 12 (3): 379-383.
10. Dahiya, R.; Singh, S. Synthesis, Characterization and Biological Activity Studies on Fanlizhicyclopeptide A. Iran. J. of Pharma. Res. 2017; 16 (3): 1178-1186.
11. Darji, N. D.; Pasha, T.Y.; Bhandri, A.; Molvi, K. I.; Desai, S. A.; Makwana, M. V. Synthesis of some novel 2, 4, 5-trisubstituted thiazoles as possible antifungal agents. J. Pharm. Res. 2011; 4: 4465-4466.
12. Dawood, K. M.; Eldebss, T. M.; El-Zahabi, S. H.; Yousef, M. H.; Metz, P. Synthesis of some new pyrazole-based 1,3-thiazoles and 1,3,4-thiadiazoles as anticancer agents. Eur J Med Chem. 2013; 70: 740-749.
13. Desai, N. C.; Bhatt, N.; Somani, H.; Trivedi, A. Synthesis, antimicrobial and cytotoxic activities of some novel thiazole clubbed 1, 3, 4-oxadiazoles. Eur. J. Med. Chem. 2013; 67: 54-59.
14. Ergenc, N.; Capan, G. Synthesis and anticonvulsant activity of new 4-thiazolidone and 4-thiazoline derivatives. Farmaco. 1994; 49: 449-451.
15. Geronikaki , A.; Vicini, P.; Dabarakis, N.; Lagunin, A.; Poroikov, V.; Dearden, J.; Modarresi, H.; Hewitt, M.; Theophilidis, G. Evaluation of the local anaesthetic activity of 3-aminobenzo[d]isothiazole derivatives using the rat sciatic nerve model. Eur. J. Med. Chem. 2009; 44: 473–481.
16. Giridhar, T.; Reddy, R. B. Aminothiazole: Part 1- Synthesis and Pharmacological evaluation of 4 (isobutylphynil) 2-substituted aminothiazoles. Ind. J. Chem. 2001; 40B: 1279-1281.
17. Gouda, M. A.; Berghot, M. A.; Baz, E. A.; Hamama, W. S. Synthesis, antitumor and antioxidant evaluation of some new thiazole and thiophene derivatives incorporated coumarin moiety. Med. Chem. Res. 2012; 21: 1062-1107.
18. Hay, M. P.; Turcotte, S,; Flanagan, J. U.; Bonnet, M.; Chan, D. A.; Sutphin, P. D.; Nguyen, P.; Giaccia, A. J.; Denny, W. A. 4-Pyridylanilinothiazoles that selectively target von Hippel-Lindau deficient renal cell carcinoma cells by inducing autophagic cell death. J Med. Chem. 2010; 53: 787-797.
19. Humphrey, J. A.; Turner, J. N.; Raymond, M. C.; Taylor, J. C. Synthesis of enantiomerically pure α-hydroxyaldehydes from the corresponding α-hydroxycarboxylic acids: novel substrates for Escherichia coli transketolase. J. Chem. Soc., Chem. Commun. 1995; 2475-2476.
20. Ibatullin, U. G.; Petrushina, T. F.; Leitis, L. Y.; Minibaev, I. Z.; Logvin, B. O. Recent Developments and Biological Activities of 2-Aminothiazole Derivatives. Chem. Heterocycl. Compd. 1993; 29: 612–615.
21. Kalhor, M.; Salehifar, M.; Nikokar, I. Synthesis, characterization, and antibacterial activities of some novel N, N-disubstituted thiourea, 2-amino thiazole and imidazole-2-thione derivatives. Med. Chem. Res. 2014; 23: 2947-2954.
22. Karegoudar, P.; Karthikeyan, M. S.; Prasad, D. J.; Mahalinga, M.; Holla, B. S. Synthesis of some novel 2, 4-disubstituted thiazoles as possible antimicrobial agents. Eur. J. Med. Chem. 2008; 43: 261-267.
23. Kreutzberger, A.; Tantawy, A. Recent Developments and Biological Activities of 2-Aminothiazole. Arch. Pharm. 1981; 314: 968- 969.
24. Kumar, Y.; Green, R.; Wise, D. S.; Wotring, L. L.; Townsend, L. B. Synthesis of 2, 4-disubstituted thiazoles and selenazoles as potential antifilarial and antitumor agents. 2. 2-arylamido and 2-alkylamido derivatives of 2-amino-4-(isothiocyanatomethyl) thiazole and 2-amino-4-(isothiocyanatomethyl) selenazole. J. Med. Chem. 1993; 36: 3849-3852.
25. Mishra, C. B.; Kumari, S. Tiwari, M. Thiazole: A promising heterocycle for the development of potent CNS active agents. Eur. J. of Med. Chem. 2015; 92: 134.
26. Omar, K.; Geronikaki, A.; Zoumpoulakis, P.; Camoutsis, C.; Sokovia, M. Novel 4-thiazolidinone derivatives as potential antifungal and antibacterial drugs. Bioorg. Med. Chem. 2010; 18: 426-432.
27. Papadopoulou, C.; Geronikaki, A.; Hadjipavlou, L. A. Synthesis and biological evaluation of new thiazolyl/benzothiazolyl-amides, derivatives of 4-phenyl-piperazine. Farmaco. 2005; 60: 969-973.
28. Romagnoli, R.; Baraldi, P. G.; Salvador, M. K.; Preti, D.; Tabrizi, M. A.; Brancale, A. Discovery and optimization of a series of 2-aryl-4-amino-5-(3, 4, 5-trimethoxybenzoyl) thiazoles as novel anticancer agents. J. Med. Chem. 2012; 55: 5433-5445.
29. Rostom, S. A. F.; Faidallah, H. M.; Radwan, M. F.; Badr, M. H. Bifunctional ethyl 2-amino-4-methylthiazole-5-carboxylate derivatives: Synthesis and in vitro biological evaluation as antimicrobial and anticancer agents. Eur. J. Med. Chem. 2014; 76: 170-181.
30. Singh, K.; Singh, S.;Taylor, J. A. Light fast monoazo dyes with an inbuilt photostabilizing unit: Synthesis and computational studies. Dyes Pigm. 2002; 54: 189–200.
31. http://www.drugbank.ca/drugs.
32. http://www.drugs.com/pro/meloxicam.
33. Winn, W.; Allen, S.; Janda, W.; Koneman, E.; Procop, G.; Schreckenberger, P.; Woods, G. Konemans Color Atlas and textbook of diagnostic microbiology. Lippincott William Wilkins Baltimore Philadelphia (6th edn.) 2006.
34. Srimanth, K.; Rao, V. R.; Krishna, D. R. Synthesis and evaluation of anticancer activity of some imidazothiazolyl, imidazobenzothiazolyl and dihydroimidazothiazolyl coumarins. Arzneimittel Forsch. 2002; 52: 388-392.
35. Tsuji, K.; Ishikawa, H. Synthesis and anti-pseudomonal activity of new 2-isocephems with a dihydroxypyridone moiety at C-7. Bioorg. Med. Chem. Lett. 1994; 4: 1601-1606.
36. Wilson, K. J.; Illig, C. R.; Subasinghe, N.; Hoffman, J. B.; Rudolph, M. J.; Soll, R.; Molloy, C. J.; Bone, R.; Green, D.; Randall, T.; Zhang, M.; Lewandowski, F. A.; Zhou, Z.; Sharp, C.; Maguire, D.; Grasberger, B.; Jarlais, R. L.; Spurlino, J. Synthesis of thiophene-2-carboxamidines containing 2-aminothiazoles and their boilogical evaluation as urokinase inhibitors. Bioorg. Med. Chem. Lett. 2001; 11: 915-918.
37. Liu, H.L.; Li, Z.; Anthonsen, T. Synthesis and Fungicidal Activity of 2-Imino-3-(4-arylthiazol-2- yl)-thiazolidin-4-ones and their 5-Arylidene Derivatives. Molecules. 2000; 5: 1055-1061.
38. Kuttan, R.; Bhanumathy, P.; Nirmala, K.; George, M. C. Potential anti-cancer activity of turmeric (Curcuma longa). Cancer Lett. 1985; 29 (2): 197-202.
39. McCauley, J.; Zivanovic, A.; Skropeta, D. Bioassays for anti-cancer activities. Methods Mol Biol. 2013; 1055: 191-205.
40. Patel, R. N.; Patel, U. Y.; Chaudhari, R. R.; Sen D. J. Synthesis and Antibacterial Study of Some New Schiff's Bases of 2-Hydrazinyl-1-(1H-Imidazole-1-yl)-Ethanone. Asian J. Research Chem. 2011; 4 (1): 55-57.
41. Manjula, S.; Devi, M. A.; Raghunandhan, N.; J. Rao, J. V. Synthesis and Pharmacological Screening of Some New Benzimidazole Derivatives. Asian J. Research Chem. 2011; 4 (1): 147-150.
42. Nagar, M. K; Waghmare, K. R.; Dhabale, P. N.; Chanekar, P. D.; Bhatia, S. Microwave Assisted Synthesis and Characterization of Phenytoin. Asian J. Research Chem. 2011; 4 (4): 619-620.
43. Shahare, H. V.; Bhoyar, P. K.; Dhabarde, D. M.; Jadhav, S. P.; Pawar, G. M. Phase Transfer Catalytic Synthesis of Aromatic Aldehydes. Research J. Pharm. and Tech. 2010; 3 (1): 275-276.
44. Selvam, T. P.; Kumar, P. V. Synthesis and Anti-hyperglycemic Activity of Novel 6,7,8,9 Tetra Hydro-5H5-Phenyl-2-Benzylidine-3-Substituted Hydrazino Thiazolo (2, 3-B) Quinazoline Derivatives and Analogues. Research J. Pharm. and Tech. 2011; 4 (1): 66-71.
45. Bhupathi, G. M.; Padmalatha, K.; Anusha, A.; Rameeza, A.; Sravanthi, M. G.; Praneetha, S. Synthesis, Characterization and Anti-microbial Activity of Acetanilide Derivatives by using Aromatic Aldehydes and Sulphonamide Derivatives. Research J. Pharm. and Tech. 2016; 9 (11): 1846-1854.
46. Dokuparthi, S. K.; Naik, J. B.; Kumar, K. S.; Saidulu, A. Synthesis, Characterization and Biological Evaluation of Benzimidazole Derivatives as Potential Anxiolytics. Research J. Pharm. and Tech. 2018; 11 (1): 221-226.
47. Sudha, R.; Nithya, G.; Kanakam, C. C. Cyclic Voltammetric Studies of Benzilic Acids and their Derivatives. Research J. Pharm. and Tech. 2018; 11 (7): 2947-2951.
48. Sudha, R; Brindha, D.P.; Nithya, G. Docking Analysis of various synthesised Benzilic acid derivatives towards Sirutin protein and toxicity studies. Research J. Pharm. and Tech. 2019; 12 (7): 3277-3281.
49. Nithya, G.; Sudha, R. Synthesis, Characterization and Study of its In Vitro Biological Activity of the compound 4,4’-Dimethoxy benzil and its Iron Oxide Nano Composite. Research J. Pharm. and Tech. 2019; 12 (11): 5524-5528.