Author(s): Abdullah Haddad, William Fraser

Email(s): aboudhaddad1@gmail.com

DOI: 10.52711/0974-360X.2021.00852   

Address: Abdullah Haddad*, William Fraser
College of Health and Life Sciences, Aston University, B4 7ET, United Kingdom.
*Corresponding Author

Published In:   Volume - 14,      Issue - 9,     Year - 2021


ABSTRACT:
The prevalence of Clostridium difficile (CD) infection has grown rapidly due to resistance and the emergence of new, highly virulent strains of the organism that have become less sensitive to many antibiotics. Vancomycin and metronidazole are front-line treatments of CD infection that still show good efficacy, but their effectiveness has declined for the treatment of recurrent infection and less sensitive strains of CD. More recently, the macrolide antibiotic fidaxomicin been introduced in the treatment of CD infection. Its high cost and limited usefulness against recurrent infection has prompted the search for new, narrow spectrum agents. We identified the CD dihydroorotate dehydrogenase (DHODase) as a potential enzyme target for the design of Knoevenagel products formed from reaction of 2-thiobarbituric acid and naphthaldehyde substrates. The presence of a hydroxyl substituent at position C2 in the naphthaldehyde ring offers the possibility to form the Knoevenagel product and to cyclize to give the tetracyclic, oxadeazaflavine with benzo-homologation. In this work, the selectivity for straight-chain formation over competing cyclisation on Knoevenagel condensation between thiobarbituric acid and naphthaldehyde substrates was examined. The outcomes of uncatalyzed condensations in refluxing ethanol were investigated by various methods including high field 1H and 13C NMR. Unsubstituted naphthaldehyde and its 2-methoxyl derivative favored straight-chain product formation whereas use of 2-hydroxynaphthaldehyde favored cyclisation and concomitant Michael addition of a second molecule of the corresponding acid to the newly formed exocyclic C=C bond. The pattern of reactivity was mirrored in the benzaldehyde series where the presence of the 2-hydroxyl function led to cyclized products with concomitant formation of the Michael adducts. The Knoevenagel products and the benzo-homologated oxadeazaflavine derivatives are candidates for evaluation as potential growth inhibitors of CD.


Cite this article:
Abdullah Haddad, William Fraser. Selectivity in the Formation of Straight-Chain Versus Cyclised products on Knoevenagel Condensation between Thiobarbituric acid and Naphthaldehydes. Research Journal of Pharmacy and Technology. 2021; 14(9):4903-8. doi: 10.52711/0974-360X.2021.00852

Cite(Electronic):
Abdullah Haddad, William Fraser. Selectivity in the Formation of Straight-Chain Versus Cyclised products on Knoevenagel Condensation between Thiobarbituric acid and Naphthaldehydes. Research Journal of Pharmacy and Technology. 2021; 14(9):4903-8. doi: 10.52711/0974-360X.2021.00852   Available on: https://rjptonline.org/AbstractView.aspx?PID=2021-14-9-66


REFERENCES:
1.    Vaishali, G.M. and Geetha, R., The superbug threat. Research Journal of Pharmacy and Technology. 2015. 8(3): p. 343-346.
2.    Shields, K., et al., Recurrent Clostridium difficile infection: from colonization to cure. Anaerobe, 2015. 34: p. 59-73.
3.    Mtsher, A.M. and Aziz, Z.S., Estimation of erythromycin and inducible clindamycin resistance in Saphylococcus aureus isolated from clinical cases. Research Journal of Pharmacy and Technology. 2020. 13(6): p. 2920-2924.
4.    Sankar, C., et al., Formulation and characterization of liposomes containing clindamycin and green tea for anti acne. Research Journal of Pharmacy and Technology. 2019. 12(12): p. 5977-5984.
5.    Deepigaa, M., Detection of Vancomycin Resistance among clinical isolates of Staphylococcus aureus. Research Journal of Pharmacy and Technology. 2018. 11(2): p. 621-623.
6.    Klimenko, L.Y., et al., New procedures of metronidazole determination by the method of gas-liquid chromatography. Research Journal of Pharmacy and Technology. 2020. 13(3): p. 1157-1166.
7.    Mohire, N.C., Yadav, A.V. and Gaikwad, V.K., Novel approaches in development of metronidazole orodispersible tablets. Research Journal of Pharmacy and Technology. 2009. 2(2): p. 283-286.
8.    Gerding, D.N., Clostridium difficile 30 years on: what has, or has not, changed and why? International Journal of Antimicrobial Agents. 2009. 33: p. S2-S8.
9.    Sreeja, M., et al., Antibiotic resistance-reasons and the most common resistant pathogens-A review. Research Journal of Pharmacy and Technology. 2017. 10(6): p. 1886-1890.
10.    Chatedaki, C., et al., Antimicrobial susceptibility and mechanisms of resistance of Greek Clostridium difficile clinical isolates. Journal of Global Antimicrobial Resistance. 2019. 16: p. 53-58.
11.    Lancaster, J.W. and Matthews, S.J., Fidaxomicin: the newest addition to the armamentarium against Clostridium difficile infections. Clinical Therapeutics. 2012. 34(1): p. 1-13.
12.    Karlowsky, J.A., Laing, N.M. and Zhanel, G.G. In vitro activity of OPT-80 tested against clinical isolates of toxin-producing Clostridium difficile. Antimicrobial Agents and Chemotherapy. 2008. 52(11): p. 4163-4165.
13.    Yanagihara, K., et al., Susceptibility of Clostridium species isolated in Japan to fidaxomicin and its major metabolite OP-1118. Journal of Infection and Chemotherapy. 2018. 24(6): p. 492-495.
14.    Enoch, D.A., et al., Real-world use of fidaxomicin in a large UK tertiary hospital: how effective is it for treating recurrent disease? Journal of Hospital Infection. 2018. 100(2): p. 142-146.
15.    Argyrou, A., Washabaugh, M.W. and Pickart, C.M., Dihydroorotate dehydrogenase from Clostridium oroticum is a class 1B enzyme and utilizes a concerted mechansim of catalysis. Biochemistry. 2000. 39(34): p. 10373-10384.
16.    Hussain, M., et al., Synthesis and antioxidant activity of novel 2-mercapto pyrimidine derivatives. Research Journal of Pharmacy and Technology, 2020. 13(3): p. 1224-1226.
17.    Inaoka, D.K., et al., Design and synthesis of potent substrate-based inhibitors of the Trypanosoma cruzi dihydroorotate dehydrogenase. Bioorganic & Medicinal Chemistry. 2017. 25(4): p. 1465-1470.
18.    Shih, K.-C., et al., Development of a human dihydroorotate dehydrogenase (hDHODH) pharma-similarity index approach with scaffold-hopping strategy for the design of novel potential inhibitors. PloS One, 2014. 9(2): p. e87960.
19.    Marcinkeviciene, J., et al., Selective inhibition of bacterial dihydroorotate dehydrogenases by thiadiazolidinediones. Biochemical Pharmacology. 2000. 60(3): p. 339-342.
20.    Srinivas, M., et al., Microwave mediated synthesis and antifungal activity of some 5-benzylidene-2,4-thiazolidinediones. Research Journal of Pharmacy and Technology, 2010. 3(2): p. 619-621.
21.    Zhang, S.-J., et al., Synthesis and antibacterial activity against Clostridium difficile of novel demethylvancomycin derivatives. Bioorganic & Medicinal Chemistry Letters. 2012. 22(15): p. 4942-4945.
22.    Fraser, W., Suckling, C.J. and Wood, H.C.S., Latent inhibitors. Part 7. Inhibition of dihydro-orotate dehydrogenase by spirocyclopropanobarbiturates. Journal of the Chemical Society, Perkin Transactions 1. 1990(11): p. 3137-3144.
23.    Deb, M. and Bhuyan, J., Uncatalyzed Knoevenagel condensation in aqueous medium at room temperature. Tetrahedron Letters. 2005. 46(38): p. 6453-6456.
24.    Levesque, D.L., et al., Synthesis of a new class of uridine phosphorylase inhibitors. Journal of Heterocyclic Chemistry. 1993. 30(5): p. 1399-1404.
25.    Figueroa-Villar, J.D. and Cruz E.R., A simple approach towards the synthesis of oxadeazaflavines. Tetrahedron, 1993. 49(14): p. 2855-2862.
26.    Abdrabaa, M.K. and Flayyih, M.T., Autolysis activity of vancomycin resistance Staphylococcus epidermidis. Asian Journal for Pharamceutical Research. 4(8): 2018.

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