Author(s)
Author(s): Ezeokonkwo Mercy A., Onwosi Ekene L., Odimegwu Damian C., Okafor Sunday N., Eze Cosmas C., Amaechi Dominic C., Attah Solomon I., Okpareke Obinna C.
Download Full PDF
Read Complete Article
DOI: 10.18483/ijSci.2420
~ 25
` 96
a 13-21
Volume 10 - Feb 2021
Abstract
A variety of butan-2-ylidene benzohydrazides were synthesized via the reaction of benzohydrazides with 4,4,4-triflouro-1-phenyl-1,-3-butanedione/4,4,4 – triflouro -1, 2, - (2 – napthyl) -1, 3 – butanedione. Acetylation and benzoylation of butan-2-ylidene benzohydrazides gave the derivatives previously unknown. The compounds were characterized by spectral analyses (Mass spec., IR, and NMR), and were evaluated for their in vitro antimicrobial activity against some clinical isolates of interest. The in vitro screening revealed that some of the compounds possessed strong inhibitory potentials against the isolates with IZD in the range of 7-14 mm. Predicted ADMET ensured the druggability properties of the synthesized compounds. The molecular docking study indicated compounds7a and 9a to possess the highest docking store and established significant interactions in the active site of the target protein.
Keywords
Butan-2-ylidene benzohydrazides, Acetylation, Benzoylation, Clinical isolates, In vitro, Drug-likeness
References
- Anto RJ, Sukumaran K, Kuttan G, Rao MNA, Subbaraju V, Kuttan R. 1995. Anticancer and antioxidant activity of synthetic chalcones and related compounds. Cancer lett 97(1): 33-37.
- Bayrak H, Demirbas A, Demirbas N, Karaoglu SA. Synthesis of some new 1, 2, 4-triazoles starting from isonicotinic acid hydrazide and evaluation of their antimicrobial activities. Eur J Med Chem 44(11): 4362-4366.
- Bourgery G, Dostert P, Lacour A, Langlois M, Pourrias B, Tisne-Versailles J. 1981. Synthesis and antiarrhythmic activity of new benzofuran derivatives. J Med Chem 24(2):159-167.
- Cassir N, Rolain JM, Brouqui P. 2014. A new strategy to fight antimicrobial resistance: the revival of old antibiotics. Front Microbial 5, 551.
- Cetinkaya Y, Falk P, Mayhall CG. 2000. Vancomycin-resistant enterococci. Clin Microbial Rev 13(4): 686-707.
- Daina A, Michielin O, Zoete V. 2017. SwissADME: a free web tool to evaluate pharmacokinetics, drug-likeness and medicinal chemistry friendliness of small molecules. Sci Rep 7(4):2717.
- Duarte CD, Tributino JL, Lacerda DI, Martins MV, Alexandre-Moreira MS, Dutra F, Calixto JB. 2007. Synthesis, pharmacological evaluation and electrochemical studies of novel 6-nitro-3, 4-methylenedioxyphenyl-N-acylhydrazone derivatives: Discovery of LASSBio-881, a new ligand of cannabinoid receptors. Bioorg Med Chem 15(6):2421-2433.
- Ezeokonkwo MA, Eze CC, Okafor SN, Onoabedje EA, Godwin-Nwakwasi EU, Ibeanu FN. 2018. Diazabenzo [a] phenoxazone sulphonamides: synthesis, in-silico and in-vitro antimicrobial studies. Med Chem Res 27(11-12):2482-2493.
- Ezeokonkwo MA, Ibeanu FN, Eze CC, Ibezim A, Ezeokoye C, Ezenwa OI, Ezeoka TV, Obiora AV. 2019. Synthesis, Antimicrobial Activity and Molecular Docking Studies of 7-Bromoquinoline-5,8-dione containing Aryl sulphonamides. Int J Appl Chem 15(2):99-112.
- Galal SA, Amira SA, Mohamed MA, Hoda I E. 2009. Synthesis of potent antitumor and antiviral benzofuran derivatives . Bioorg med Chem Lett 19(9): 2420-2428.
- Gulshan K, Moye-Rowley WS. 2007. Multidrug resistance in fungi. Eukaryot cell 6(11): 1933-1942.
- Khan MW, Alam MJ, Rashid MA. 2005. A new structural alternative in benzo [b] furans for antimicrobial activity. Bioorg Med Chem 13(16): 4796-4805.
- Kirilmis C, Ahmedzade M, Servi S, Koca M, Kizirgil A, Kazaz C. 2008. Synthesis and antimicrobial activity of some novel derivatives of benzofuran: Part 2. The synthesis and antimicrobial activity of some novel 1-(1-benzofuran-2-yl)-2-mesitylethanone derivatives. Eur J Med Chem 43(2): 300-308.
- Klenke B, Barrett MP, Brun R, Gilbert IH. 2003. Antiplasmodial activity of a series of 1, 3, 5-triazine-substituted polyamines. J Antimicrob Chemother 52: 290–293.
- Koçyiğit-Kaymakçıoğlu B, Oruç-Emre EE, Ünsalan S, Tabanca N, Khan SI, Wedge DE, Rollas S. 2012. Synthesis and biological activity of hydrazide–hydrazones and their corresponding 3-acetyl-2, 5-disubstituted-2, 3-dihydro-1, 3, 4-oxadiazoles. Med Chem Res, 21(11):3499-3508.
- Kömürcü ŞG, Rollas S, Ülgen M, Gorrod JW, Çevikbaş A. 1995. Evaluation of some arylhydrazones of p-aminobenzoic acid hydrazide as antimicrobial agents and their in vitro hepatic microsomal metabolism. Boll Chim Farm 134:375-379.
- Lengaur T, Rarey M. 1996. Computational method for biomolecular docking. Curr Opin Strut Biol 6(3):402-6.
- Li R, Kenyon GL, Cohen FE, Chen X, Gong B, Dominguez JN, Rosenthal PJ. 1995. In vitro antimalarial activity of chalcones and their derivatives. J Med Chem 38(26):5031-5037.
- Lipinski CA. 2000. Drug-like properties and the causes of poor solubility and poor permeability. J pharmacol Toxicol Meth 44(1):235-249.
- Mishra SK, Rijal BP, Pokhrel BM. 2013. Emerging threat of multidrug resistant bugs–Acinetobacter calcoaceticus baumannii complex and methicillin resistant Staphylococcus aureus . BMC res notes 6(1): 98.
- Mukherjee S, Kumar V, Prasad AK, Raj HG, Bracke ME, Olsen CE, Parmar VS. 2001. Synthetic and biological activity evaluation studies on novel 1, 3-diarylpropenones . Bioorg Med Chem 9(2): 337-345.
- Narasimhan B, Judge V, Narang R, Ohlan R, Ohlan S. 2007. Quantitative structure–activity relationship studies for prediction of antimicrobial activity of synthesized 2, 4-hexadienoic acid derivatives. Bioorg Med Chem Lett 17(21):5836-5845.
- Nielsen SF, Christensen SB, Cruciani G, Kharazmi A, Liljefors T. 1998. Antileishmanial chalcones: Statistical design, synthesis, and three-dimensional quantitative structure−activity relationship analysis. J Med Chem 41(24): 4819-4832.
- Osório TM, Delle Monache F, Chiaradia LD, Mascarello A, Stumpf TR, Zanetti CR, Garcia L A. 2002. Antibacterial activity of chalcones, hydrazones and oxadiazoles against methicillin-resistant Staphylococcus aureus. Bioorg Med Chem Lett 22(1): 225-230.
- Reetu VK. 2012. Computer aided design of selective calcium channel blockers: using pharmacophore - based and docking simulations. Indian J Pharm Sci Res 3(3): 805-10.
- Rollas S, Gulerman N, Erdeniz H. 2002. Synthesis and antimicrobial activity of some new hydrazones of 4-fluorobenzoic acid hydrazide and 3-acetyl-2, 5-disubstituted-1, 3, 4-oxadiazolines. Il Farmaco 57(2): 171-174.
- Sridhar P, Alagumuthu M, Arumugam S, Reddy SR. 2016. Synthesis of quinoline acetohydrazide-hydrazone derivatives evaluated as DNA gyrase inhibitors and potent antimicrobial agents. RSC advances 6(69):64460-64468.
- Sriram D, Yogeeswari P, Devakaram RV. 2006. Synthesis, in vitro and in vivo antimycobacterial activities of diclofenac acid hydrazones and amides. Bioorg Med Chem 14(9):3113-3118.
- Tanoli S, Tanoli N, Usmani S, Ferreira A. 2014. The exploration of interaction studies of smaller size, mostly ignored yet intrinsically inestimable molecules towards BSA; An example of STD and DOSY NMR. Open Chem 12(3):332-340.
- Trott O, Olson AJ. 2010. AutoDock Vina: Improving the speed and accuracy of docking with a new scoring function, efficient optimization, and multithreading. J Comp Chem 31(2):455-461.
- Ulgen M, Durgun BB, Rollas S, Gorrod JW. 1997. The in vitro hepatic microsomal metabolism of benzoic acid benzylidenehydrazide. Drug Metabol Drug Inter13(4):285-294.
- Veber DF, Johnson SR, Cheng HY, Smith BR, Ward KW, Kopple KD. 2002. Molecular properties that influence the oral bioavailability of drug candidates. J Med Chem 45(12):2615-2623
- Veeramanikandan S, Benita Sherine H. 2015. Synthesis, characterization and biological applications of substituted benzohydrazide derivatives. Der Pharma Chem 7:70-84.
Cite this Article:
International Journal of Sciences is Open Access Journal.
This article is licensed under a Creative Commons Attribution 4.0 International (CC BY 4.0) License.
Author(s) retain the copyrights of this article, though, publication rights are with Alkhaer Publications.