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Medicinal Chemistry

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ISSN (Print): 1573-4064
ISSN (Online): 1875-6638

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Research Article

Synthesis and Antimicrobial Activity of Novel 1, 2, 4-Triazolopyrimidofuroquinazolinones from Natural Furochromones (Visnagenone and Khellinone)

Author(s): Ameen A. Abu-Hashem*, Hoda A.R. Hussein and Ahmed S. Aly

Volume 17, Issue 7, 2021

Published on: 06 April, 2020

Page: [707 - 723] Pages: 17

DOI: 10.2174/1573406416666200406130047

Price: $65

Abstract

Background: Previous and recent scientific research has shown that triazolopyrimidine and furochromones have a wide range of pharmacological activities for the treatment of numerous diseases, including anticancer, antiviral, anti-depressant, anti-microbial, anti-inflammatory, and analgesic activities.

Objective: Preparation of new drugs derived from a natural furochromones as (1-hydrazinyl or methylthio),-furopyrimidoquinazolinone, 1, 2, 4-triazolopyrimidofuroquinazolin-5-one, and quinazoline- pyrimidofuro- quinazoline-8, 10-dione and the study of their biological activity as antimicrobial agents.

Methods: A series of novel N’-furopyrimidoquinazoline-hydrazide; 1, 2, 4-triazolopyrimidofuroquinazolin- 5-one; furopyrimidoquinazolin-3-one and quinazoline-pyrimidofuroquinazoline-8, 10- dione derivatives were synthesized from substituted (methylthio)-furopyrimidoquinazolinone (3ab) and 1-hydrazinyl-furopyrimido- quinazolinone (4a-b) as the starting material.

Results: All compounds were synthesized in good yields (71-95%) in a gradually efficient system under mild condition and some of the procedures were used such as microwave oven. The new compounds have been confirmed by means of different spectroscopic methods such as IR, 1D and 2D -NMR techniques and mass spectrum. The in vitro antimicrobial activities were evaluated for the prepared compounds using many types of bacteria (Gram-positive and Gram-negative) and fungi.

Conclusion: 1, 2, 4-triazolopyrimidofuroquinazolin-5-one derivatives (10a-f, 8a-b, 7a-b and 6a-d) showed the most efficient antimicrobial activities compared with the cefotaxime sodium and nystatin as standard drugs.

Keywords: Visnagenone, khellinone, hydrazide, 1, 2, 4-triazolopyrimidine, benzylidene, furoquinazolinones, antimicrobial activity.

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[1]
Vedaldi, D.; Caffieri, S.; Dall’Acqua, F.; Andreassi, L.; Bovalini, L.; Martelli, P. Khellin, a naturally occurring furochromone, used for the photochemotherapy of skin diseases: mechanism of action. Farmaco, Sci., 1988, 43(4), 333-346.
[PMID: 3203737]
[2]
Bhagavathula, A.S.; Mahmoud Al-Khatib, A.J.; Elnour, A.A.; Al Kalbani, N.M.; Shehab, A. Ammi Visnaga in treatment of urolithiasis and hypertriglyceridemia. Pharmacognosy Res., 2014, 7(4), 397-400.
[PMID: 26692756]
[3]
Gammill, R.B.; Day, C.E.; Schurr, P.E. Khellin analogues. 1. General topological requirements for lipid-altering activity in furochromones. J. Med. Chem., 1983, 26(12), 1672-1674.
[http://dx.doi.org/10.1021/jm00366a002] [PMID: 6644736]
[4]
Abu-Hashem, A.A.; El-Shazly, M. Synthesis, reactions and biological activities of furochromones: a review. Eur. J. Med. Chem., 2015, 90, 633-665.
[http://dx.doi.org/10.1016/j.ejmech.2014.12.001] [PMID: 25499986]
[5]
Kim, S.; Salim, A.A.; Swanson, S.M.; Kinghorn, A.D. Potential of cyclopenta[b]benzofurans from Aglaia species in cancer chemotherapy. Anticancer. Agents Med. Chem., 2006, 6(4), 319-345.
[http://dx.doi.org/10.2174/187152006777698123] [PMID: 16842234]
[6]
Hudson, J.B.; Towers, G.H.N. Phytomedicines as antivirals. Drugs Future, 1999, 24, 295-320.
[http://dx.doi.org/10.1358/dof.1999.024.03.858620]
[7]
Kandil, A.; Gobran, W.; Samaan, H.A.; Abu-Shady, H. The spasmolytic potential of a new khellin derivative. J. Drug Res., 1977, 9, 35.
[8]
Oguro, K.; Hashimoto, K. Quantitative and comparative studies of pharmacological features in the coronary, femoral and renal circulations with different coronary vasodilators. Jpn. J. Pharmacol., 1974, 24(2), 227-233.
[http://dx.doi.org/10.1254/jjp.24.227] [PMID: 4212295]
[9]
El-Nakkady, S.S.; Roaiah, H.F.; El-Serwy, W.S.; Soliman, A.M.; El-Moez, S.I.; Abdel-Rahman, A.A. Antitumor and antimicrobial activities of some hetero aromatic benzofurans derived from naturally occurring visnagin. Acta Pol. Pharm., 2012, 69(4), 645-655.
[PMID: 22876607]
[10]
Rescifina, A.; Chiacchio, M.A.; Corsaro, A.; De Clercq, E.; Iannazzo, D.; Mastino, A.; Piperno, A.; Romeo, G.; Romeo, R.; Valveri, V. Synthesis and biological activity of isoxazolidinyl polycyclic aromatic hydrocarbons: potential DNA intercalators. J. Med. Chem., 2006, 49(2), 709-715.
[http://dx.doi.org/10.1021/jm050772b] [PMID: 16420056]
[11]
Abd Elhafez, O.M. El Khrisy, Eel.D.; Badria, F.; Fathy, Ael.D. Synthesis and biological investigations of new thiazolidinone and oxadiazoline coumarin derivatives. Arch. Pharm. Res., 2003, 26(9), 686-696.
[http://dx.doi.org/10.1007/BF02976675] [PMID: 14560914]
[12]
Kamal, A.; Shankaraiah, N.; Prabhakar, S.; Reddy, ChR.; Markandeya, N.; Reddy, K.L.; Devaiah, V. Solid-phase synthesis of new pyrrolobenzodiazepine-chalcone conjugates: DNA-binding affinity and anticancer activity. Bioorg. Med. Chem. Lett., 2008, 18(7), 2434-2439.
[http://dx.doi.org/10.1016/j.bmcl.2008.02.047] [PMID: 18325766]
[13]
Abu-Hashem, A.A.; Youssef, M.M. Synthesis of new visnagen and khellin furochromone pyrimidine derivatives and their anti-inflammatory and analgesic activity. Molecules, 2011, 16(3), 1956-1972.
[http://dx.doi.org/10.3390/molecules16031956] [PMID: 21358587]
[14]
Abu-Hashem, A.A.; El-Shazly, M. Synthesis of new quinoxaline, pyrimidine, and pyrazole furochromone derivatives as cytotoxic agents. Monatsh. Chem., 2017, 148, 1853-1863.
[http://dx.doi.org/10.1007/s00706-017-1960-6]
[15]
Keshk, E.M.; Abu-Hashem, A.A.; Girges, M.M.; Abdel-Rahman, A.H.; Badria, F.A. Synthesis of benzo[1,2-b:5,4-b]difuranyl-triazoles, oxadiazoles, thiazolidione, thiadiazoles,and the use of DNA in evaluation of their biological activity. Phosphorus. Sulufer Silicon, 2004, 179, 1577-1593.
[http://dx.doi.org/10.1080/10426500490464140]
[16]
Abu-Hashem, A.A. Synthesis of new furothiazolo pyrimido quinazolinones from visnagenone or khellinone and antimicrobial activity. Molecules, 2018, 23(11), 2793.
[http://dx.doi.org/10.3390/molecules23112793] [PMID: 30373270]
[17]
Burguete, A.; Pontiki, E.; Hadjipavlou-Litina, D.; Villar, R.; Vicente, E.; Solano, B.; Ancizu, S.; Pérez-Silanes, S.; Aldana, I.; Monge, A. Synthesis and anti-inflammatory/antioxidant activities of some new ring substituted 3-phenyl-1-(1,4-di-N-oxide quinoxalin-2-yl)-2-propen-1-one derivatives and of their 4,5-dihydro-(1H)-pyrazole analogues. Bioorg. Med. Chem. Lett., 2007, 17(23), 6439-6443.
[http://dx.doi.org/10.1016/j.bmcl.2007.10.002] [PMID: 17942306]
[18]
Mashevskaya, I.V.; Makhmudov, R.R.; Aleksandrova, G.A.; Duvalov, A.V.; Maslivets, A.N. Synthesis, analgesic, and antibacterial activity of the products of interaction of hetereno[a]-dihydro-2,3-pyrrolediones with phenylhydrazines. Pharm. Chem. J., 2001, 35, 69-71.
[http://dx.doi.org/10.1023/A:1010464619724]
[19]
Cheeseman, G.W.H.; Cookson, R.F. In the chemistry of heterocyclic compounds;; Weissberger, A.; Taylor, E.C., Eds.; J. Wiley & Sons:: New York, 1979, 35, pp. 1-27. 35-.
[20]
Porter, A.E.A. In comprehensive heterocyclic chemistry;; Katrizky, A. R.; Rees, C.W., Eds.; Pergamon: New York, 1984.
[21]
Sarges, R.; Howard, H.R.; Browne, R.G.; Lebel, L.A.; Seymour, P.A.; Koe, B.K. 4-Amino[1,2,4]triazolo[4,3-a]quinoxalines. A novel class of potent adenosine receptor antagonists and potential rapid-onset antidepressants. J. Med. Chem., 1990, 33(8), 2240-2254.
[http://dx.doi.org/10.1021/jm00170a031] [PMID: 2374150]
[22]
Rangisetty, J.B.; Gupta, C.N.V.H.B.; Prasad, A.L.; Srinivas, P.; Sridhar, N.; Parimoo, P.; Veeranjaneyulu, A. Synthesis of new arylaminoquinoxalines and their antimalarial activity in mice. J. Pharm. Pharmacol., 2001, 53(10), 1409-1413.
[http://dx.doi.org/10.1211/0022357011777765] [PMID: 11697550]
[23]
Tandon, V.K.; Yadav, D.B.; Maurya, H.K.; Chaturvedi, A.K.; Shukla, P.K. Design, synthesis, and biological evaluation of 1,2,3-trisubstituted-1,4-dihydrobenzo[g]quinoxaline-5,10-diones and related compounds as antifungal and antibacterial agents. Bioorg. Med. Chem., 2006, 14(17), 6120-6126.
[http://dx.doi.org/10.1016/j.bmc.2006.04.029] [PMID: 16806945]
[24]
Srinivas, C.; Kumar, C.N.S.P.; Rao, V.J.; Palaniappan, S. Green approach for the synthesis of quinoxaline derivatives in water medium using reusable polyaniline sulfate salt catalyst and sodium laurylsulfate. Catal. Lett., 2008, 121, 291-296.
[http://dx.doi.org/10.1007/s10562-007-9335-y]
[25]
Dell, A.; Williams, D.H.; Morris, H.R.; Smith, G.A.; Feeney, J.; Roberts, G.C.K. Structure revision of the antibiotic echinomycin. J. Am. Chem. Soc., 1975, 97(9), 2497-2502.
[http://dx.doi.org/10.1021/ja00842a029] [PMID: 1133418]
[26]
El-Gendy, M.M.A.; Shaaban, M.; Shaaban, K.A.; El-Bondkly, A.M.; Laatsch, H. Essramycin: a first triazolopyrimidine antibiotic isolated from nature. J. Antibiot. (Tokyo), 2008, 61(3), 149-157.
[http://dx.doi.org/10.1038/ja.2008.124] [PMID: 18503193]
[27]
Abu-Hashem, A.A.; Hussein, H.A.R.; Abu-zied, Kh.M. Synthesis of novel 1, 2, 4-triazolopyrimidines and their evaluation as antimicrobial agents. Med. Chem. Res., 2016, 26, 120-130.
[http://dx.doi.org/10.1007/s00044-016-1733-5]
[28]
Abu-Hashem, A.A.; Goud, M.A. Synthesis and antimicrobial activity of some novel quinoline, chromene, pyrazole derivatives bearing triazolopyrimidine moiety. J. Heterocycl. Chem., 2017, 54, 850-858.
[http://dx.doi.org/10.1002/jhet.2645]
[29]
Shaaban, M.R.; Saleh, T.S.; Mayhoub, A.S.; Mansour, A.; Farag, A.M. Synthesis and analgesic/anti-inflammatory evaluation of fused heterocyclic ring systems incorporating phenylsulfonyl moiety. Bioorg. Med. Chem., 2008, 16(12), 6344-6352.
[http://dx.doi.org/10.1016/j.bmc.2008.05.011] [PMID: 18502132]
[30]
Beyer, C.F.; Zhang, N.; Hernandez, R.; Vitale, D.; Lucas, J.; Nguyen, T.; Discafani, C.; Ayral-Kaloustian, S.; Gibbons, J.J. TTI-237: a novel microtubule-active compound with in vivo antitumor activity. Cancer Res., 2008, 68(7), 2292-2300.
[http://dx.doi.org/10.1158/0008-5472.CAN-07-1420] [PMID: 18381436]
[31]
Fischer, G. Recent progress in 1, 2, 4-triazolo [1, 5-a] pyrimidine chemistry. Adv. Heterocycl. Chem., 2008, 95, 143-219.
[http://dx.doi.org/10.1016/S0065-2725(07)95003-5]
[32]
Li, H.; Tatlock, J.; Linton, A.; Gonzalez, J.; Jewell, T.; Patel, L.; Ludlum, S.; Drowns, M.; Rahavendran, S.V.; Skor, H.; Hunter, R.; Shi, S.T.; Herlihy, K.J.; Parge, H.; Hickey, M.; Yu, X.; Chau, F.; Nonomiya, J.; Lewis, C. Discovery of (R)-6-cyclopentyl-6-(2-(2,6-diethylpyridin-4-yl)ethyl)-3-((5,7-dimethyl-[1,2,4]triazolo[1,5-a]pyrimidin-2-yl)methyl)-4-hydroxy-5,6-dihydropyran-2-one (PF-00868554) as a potent and orally available hepatitis C virus polymerase inhibitor. J. Med. Chem., 2009, 52(5), 1255-1258.
[http://dx.doi.org/10.1021/jm8014537] [PMID: 19209845]
[33]
Abu-Hashem, A.A. Synthesis and biological activity of pyrimidines, quinolines, thiazines and pyrazoles bearing a common thieno moiety. Acta. Pol. Pharm. Drug Res. (Stuttg.), 2018, 75(1), 59-70.
[34]
Jain, S.R.; Kar, A. The antibacterial activity of some essential oils and their combinations. Planta Med., 1971, 20(2), 118-123.
[http://dx.doi.org/10.1055/s-0028-1099675] [PMID: 5119010]
[35]
el-Gazzar, A.B.A.; Hafez, H.N.; Nawwar, G.A.M. New acyclic nucleosides analogues as potential analgesic, anti-inflammatory, anti-oxidant and anti-microbial derived from pyrimido[4,5-b]quinolines. Eur. J. Med. Chem., 2009, 44(4), 1427-1436.
[http://dx.doi.org/10.1016/j.ejmech.2008.09.030] [PMID: 18977557]
[36]
El-Gazzar, A.B.A.; Gaafar, A.M.; Youssef, M.M.; Abu-Hashem, A.A.; Badria, F.A. Synthesis and anti-oxidant activity of novel pyrimido[4,5-b]quinolin-4-one derivatives with a new ring system. Phosphorus Sulfur, 2007, 182(9), 2009-2037.
[http://dx.doi.org/10.1080/10426500701369864]

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