Login Register Cart 0
Generic placeholder image

Letters in Drug Design & Discovery

Editor-in-Chief

ISSN (Print): 1570-1808
ISSN (Online): 1875-628X

Back
Research Article

Biology-oriented Drug Synthesis (BIODS), Structural Characterization and Bioactivities of Novel Albendazole Derivatives

Author(s): Momin Khan*, Shahid Khan, Uzma Salar, Khalid Mohammed Khan, Gauhar Rehman, Naeem Gul and Iltaf Khan

Volume 16, Issue 12, 2019

Page: [1329 - 1338] Pages: 10

DOI: 10.2174/1570180816666190221163641

Price: $65

Abstract

Background: Albendazole is a drug, belongs to the family of benzimidazole, and used as an anthelmintic agent in both human and veterinary medicine. It is marketed as Albenza which is used for the treatment of a variety of parasitic worm infestations such as roundworms, tapeworms, and flukes. In recent past, we have reported various classes of compounds as anti-glycating agents, in continuation of Biology-oriented Drug Synthesis (BIODS), seventeen albendazole derivatives 2-18 were synthesized evaluated for yeast glucose uptake activity.

Methods: In the present study, Albendazole (2 g, 7.5 mmol), potassium hydroxide (3 g) were dissolved in ethanol (50 mL) into a 250 mL round-bottomed flask and refluxed for 48 h. TLC (ethyl acetate: hexane, 6:4) was monitored in order to check the reaction progress. After completion, the reaction mixture was dried under air and washed with an excess of distilled water. Precipitates were dried and crystallized from ethanol. The product was characterized by EI-MS and 1H-NMR.

Results: Our present study showed that all compounds showed a varying degree of yeast glucose uptake activity ranging between IC50 = 51.41-258.40 µM, compared with standard metronidazole (IC50 = 41.86 ± 0.09 µM). This study has identified a series of potential leads for anti-glycating agents.

Conclusion: Biology-oriented drug synthesis and in vitro yeast glucose uptake activity of albendazole derivatives gave rise to a number of lead molecule such as 3 (IC50 = 59.37 ± 0.26 µM), 5 (IC50 = 59.70 ± 0.32 µM), 6 (IC50 = 60.78 ± 0.54 µM), 8 (IC50 = 54.61 ± 0.20 µM), 16 (IC50 = 56.57 ± 0.04 µM) and 14 (IC50 = 51.41 ± 1.25 µM).

Keywords: Biology-oriented Drug Synthesis (BIODS), albendazole, yeast glucose uptake, substituted benzoyl chlorides, substituted benzoic acids, hyperglycemia.

« Previous Next »
Graphical Abstract

[1]
Bauer, C.; Gey, A. Efficacy of six anthelmintics against luminal stages of Baylisascaris procyonis in naturally infected raccoons (Procyon lotor). Vet. Parasitol., 1995, 60(1-2), 155-159.
[http://dx.doi.org/10.1016/0304-4017(94)00774-7] [PMID: 8644451]
[2]
Anderson, A.; Boomer, B.B. Family Feud.; Bowker Magazine Group Cahners Magazine Division;, 249 W 17th St, New York, Ny 10011,; 1994119. , p. 70.
[3]
Wank, S.A. G protein-coupled receptors in gastrointestinal physiology. I. CCK receptors: An exemplary family. Am. J. Physiol., 1998, 274(4 Pt 1), G607-G613.
[PMID: 9575840]
[4]
Kumar, D.; Jacob, M.R.; Reynolds, M.B.; Kerwin, S.M.; Kerwin, S.M. Synthesis and evaluation of anticancer benzoxazoles and benzimidazoles related to UK-1. Bioorg. Med. Chem., 2002, 10(12), 3997-4004.
[http://dx.doi.org/10.1016/S0968-0896(02)00327-9] [PMID: 12413851]
[5]
Tiwari, A.K.; Mishra, A.K.; Bajpai, A.; Mishra, P.; Singh, S.; Sinha, D.; Singh, V.K. Synthesis and evaluation of novel benzimidazole derivative [Bz-Im] and its radio/biological studies. Bioorg. Med. Chem. Lett., 2007, 17(10), 2749-2755.
[http://dx.doi.org/10.1016/j.bmcl.2007.02.071] [PMID: 17368898]
[6]
Arjmand, F.; Mohani, B.; Ahmad, S. Synthesis, antibacterial, antifungal activity and interaction of CT-DNA with a new benzimidazole derived Cu(II) complex. Eur. J. Med. Chem., 2005, 40(11), 1103-1110.
[http://dx.doi.org/10.1016/j.ejmech.2005.05.005] [PMID: 16006016]
[7]
Kühler, T.C.; Swanson, M.; Shcherbuchin, V.; Larsson, H.; Mellgârd, B.; Sjöström, J.E. Structure-activity relationship of 2-[[(2-pyridyl)methyl]thio]-1H- benzimidazoles as anti Helicobacter pylori agents in vitro and evaluation of their in vivo efficacy. J. Med. Chem., 1998, 41(11), 1777-1788.
[http://dx.doi.org/10.1021/jm970165r] [PMID: 9599229]
[8]
Horn, J. The proton-pump inhibitors: Similarities and differences. Clin. Ther., 2000, 22(3), 266-280.
[http://dx.doi.org/10.1016/S0149-2918(00)80032-6] [PMID: 10963283]
[9]
Kazimierczuk, Z.; Upcroft, J.A.; Upcroft, P.; Górska, A.; Starościak, B.; Laudy, A. Synthesis, antiprotozoal and antibacterial activity of nitro- and halogeno-substituted benzimidazole derivatives. Acta Biochim. Pol., 2002, 49(1), 185-195.
[PMID: 12136939]
[10]
Elnima, E.I.; Zubair, M.U.; Al-Badr, A.A. Antibacterial and antifungal activities of benzimidazole and benzoxazole derivatives. Antimicrob. Agents Chemother., 1981, 19(1), 29-32.
[http://dx.doi.org/10.1128/AAC.19.1.29] [PMID: 7247359]
[11]
Göker, H.; Tunçbilek, M.; Ayhan, G.; Altanlar, N. Synthesis of some new benzimidazole-carboxamides and evaluation of their antimicrobial activity. Farmaco, 1998, 53(6), 415-420.
[http://dx.doi.org/10.1016/S0014-827X(98)00045-7] [PMID: 9764474]
[12]
Nguyen, P.T.M.; Baldeck, J.D.; Olsson, J.; Marquis, R.E. Antimicrobial actions of benzimidazoles against oral streptococci. Oral Microbiol. Immunol., 2005, 20(2), 93-100.
[http://dx.doi.org/10.1111/j.1399-302X.2004.00197.x] [PMID: 15720569]
[13]
Boiani, M.; González, M. Imidazole and benzimidazole derivatives as chemotherapeutic agents. Mini Rev. Med. Chem., 2005, 5(4), 409-424.
[http://dx.doi.org/10.2174/1389557053544047] [PMID: 15853629]
[14]
Veerakumari, L.; Munuswamy, N. In vitro effect of some anthelmintics on lactate dehydrogenase activity of Cotylophoron cotylophorum (Digenea: Paramphistomidae). Vet. Parasitol., 2000, 91(1-2), 129-140.
[http://dx.doi.org/10.1016/S0304-4017(00)00258-2] [PMID: 10889365]
[15]
Merino, G.; Jonker, J.W.; Wagenaar, E.; Pulido, M.M.; Molina, A.J.; Alvarez, A.I.; Schinkel, A.H. Transport of anthelmintic benzimidazole drugs by breast cancer resistance protein (BCRP/ABCG2). Drug Metab. Dispos., 2005, 33(5), 614-618.
[http://dx.doi.org/10.1124/dmd.104.003319] [PMID: 15703302]
[16]
Iemura, R.; Kawashima, T.; Fukuda, T.; Ito, K.; Tsukamoto, G. Synthesis of 2-(4-substituted-1-piperazinyl)benzimidazoles as H1-antihistaminic agents. J. Med. Chem., 1986, 29(7), 1178-1183.
[http://dx.doi.org/10.1021/jm00157a010] [PMID: 2879912]
[17]
Cole, E.R.; Crank, G.; Salam-Sheikh, A. Antioxidant properties of benzimidazoles. J. Agric. Food Chem., 1974, 22(5), 918.
[http://dx.doi.org/10.1021/jf60195a022] [PMID: 4423283]
[18]
Kuş, C.; Ayhan-Kilcigil, G.; Can Eke, B.; Işcan, M. Synthesis and antioxidant properties of some novel benzimidazole derivatives on lipid peroxidation in the rat liver. Arch. Pharm. Res., 2004, 27(2), 156-163.
[http://dx.doi.org/10.1007/BF02980099] [PMID: 15022715]
[19]
Temiz-Arpaci, O.; Coban, T.; Tekiner-Gulbas, B.; Can-Eke, B.; Yildiz, I.; Aki-Sener, E.; Yalcin, I.; Iscan, M. A study on the antioxidant activities of some new benzazole derivatives. Acta Biol. Hung., 2006, 57(2), 201-209.
[http://dx.doi.org/10.1556/ABiol.57.2006.2.7] [PMID: 16841471]
[20]
Ateş-Alagöz, Z.; Kuş, C.; Coban, T. Synthesis and antioxidant properties of novel benzimidazoles containing substituted indole or 1,1,4,4-tetramethyl-1,2,3,4-tetrahydro-naphthalene fragments. J. Enzyme Inhib. Med. Chem., 2005, 20(4), 325-331.
[http://dx.doi.org/10.1080/14756360500131706] [PMID: 16206826]
[21]
Kumar, J.R.; Jat, J.L.; Pathak, D.P. Synthesis of benzimidazole derivatives: As antihypertensive agents E. J. Chem., 2006, 3, 278.
[22]
Achar, K.C.S.; Hosamani, K.M.; Seetharamareddy, H.R. In vivo analgesic and anti-inflammatory activities of newly synthesized benzimidazole derivatives. Eur. J. Med. Chem., 2010, 45(5), 2048-2054.
[http://dx.doi.org/10.1016/j.ejmech.2010.01.029] [PMID: 20133024]
[23]
Zhao, Z.; Arnaiz, D.O.; Griedel, B.; Sakata, S.; Dallas, J.L.; Whitlow, M.; Trinh, L.; Post, J.; Liang, A.; Morrissey, M.M.; Shaw, K.J. Design, synthesis, and in vitro biological activity of benzimidazole based factor Xa inhibitors. Bioorg. Med. Chem. Lett., 2000, 10(9), 963-966.
[http://dx.doi.org/10.1016/S0960-894X(00)00139-6] [PMID: 10853669]
[24]
(a) Kamal, A.; Kumar, P.P.; Sreekanth, K.; Seshadri, B.N.; Ramulu, P. Synthesis of new benzimidazole linked pyrrolo [2,1-c] [1,4]benzodiazepine conjugates with efficient DNA-binding affinity and potent cytotoxicity. Bioorg. Med. Chem. Lett., 2008, 18(8), 2594-2598.
[http://dx.doi.org/10.1016/j.bmcl.2008.03.039] [PMID: 18378445]
(b) Garuti, L.; Roberti, M.; Malagoli, M.; Rossi, T.; Castelli, M. Synthesis and Antiproliferative activity of some benzimidazole-4,7-dione derivatives. Bioorg. Med. Chem. Lett., 2000, 10(19), 2193-2195.
[http://dx.doi.org/10.1016/S0960-894X(00)00429-7] [PMID: 11012027]
[25]
Budow, S.; Kozlowska, M.; Gorska, A.; Kazimierczuk, Z.; Eickmeier, H.; Colla, P.L.; Gosselin, G.; Seela, F. Substituted benzimidazoles: antiviral activity and synthesis of nucleosides. ARKIVOC, 2009, 3, 225.
[26]
Ishida, T.; Suzuki, T.; Hirashima, S.; Mizutani, K.; Yoshida, A.; Ando, I.; Ikeda, S.; Adachi, T.; Hashimoto, H. Benzimidazole inhibitors of hepatitis C virus NS5B polymerase: Identification of 2-[(4-diarylmethoxy)phenyl]-benzimidazole. Bioorg. Med. Chem. Lett., 2006, 16(7), 1859-1863.
[http://dx.doi.org/10.1016/j.bmcl.2006.01.032] [PMID: 16455252]
[27]
Garuti, L.; Roberti, M.; Gentilomi, G. Synthesis and antiviral assays of some benzimidazole nucleosides and acyclonucleosides. Farmaco, 2001, 56(11), 815-819.
[http://dx.doi.org/10.1016/S0014-827X(01)01164-8] [PMID: 11765032]
[28]
Biron, K.K.; Harvey, R.J.; Chamberlain, S.C.; Good, S.S.; Smith, A.A., III; Davis, M.G.; Talarico, C.L.; Miller, W.H.; Ferris, R.; Dornsife, R.E.; Stanat, S.C.; Drach, J.C.; Townsend, L.B.; Koszalka, G.W. Potent and selective inhibition of human cytomegalovirus replication by 1263W94, a benzimidazole L-riboside with a unique mode of action. Antimicrob. Agents Chemother., 2002, 46(8), 2365-2372.
[http://dx.doi.org/10.1128/AAC.46.8.2365-2372.2002] [PMID: 12121906]
[29]
Mason, J.S.; Morize, I.; Menard, P.R.; Cheney, D.L.; Hulme, C.; Labaudiniere, R.F. New 4-point pharmacophore method for molecular similarity and diversity applications: Overview of the method and applications, including a novel approach to the design of combinatorial libraries containing privileged substructures. J. Med. Chem., 1999, 42(17), 3251-3264.
[http://dx.doi.org/10.1021/jm9806998] [PMID: 10464012]
[30]
Gezginci-Oktayoglu, S.; Basaraner, H.; Yanardag, R.; Bolkent, S. The effects of combined treatment of antioxidants on the liver injury in STZ diabetic rats. Dig. Dis. Sci., 2009, 54(3), 538-546.
[http://dx.doi.org/10.1007/s10620-008-0381-0] [PMID: 18712602]
[31]
Kavishankar, G.B.; Lakshmidevi, N.; Murthy, M.; Prakash, S.R. Diabetes and medicinal plants-A Review. Int. J. Pharma Bio Sci., 2011, 2, 65.
[32]
Akanksha, S.A.K.; Srivastava, A.K.; Maurya, R. Antihyperglycemic activity of compounds isolated from Indian medicinal plants. Indian J. Exp. Biol., 2010, 48(3), 294-298.
[PMID: 21046984]
[33]
Bandawane, D.; Juvekar, A.; Juvekar, M. Antidiabetic and antihyperlipidemic effect of Alstonia scholaris Linn bark in streptozotocin induced diabetic rats. Indian J. Pharm. Educ. Res., 2011, 45, 114.
[34]
(a) Bano, B.; Abbasi, S.; Khan, J.A.J.; Hussain, S.; Rasheed, S.; Perveen, S.; Khan, K.M.; Choudhary, M.I. Antiglycation activity of quinoline derivatives- A new therapeutic class for the management of type 2 diabetes complications. Med. Chem., 2014, 11, 60.
(b) Abbasi, S.; Mirza, S.; Rasheed, S.; Hussain, S.; Khan, J.A.J.; Khan, K.M.; Perveen, S.; Choudhary, M.I. Benzothiazole derivatives: Novel inhibitors of methylglyoxal mediated glycation of protein in vitro. Med. Chem., 2014, 10, 824.
(c) Khan, K.M.; Irfan, M.; Ashraf, M.; Taha, M.; Saad, S.M.; Perveen, S.; Choudhary, M.I. Synthesis of phenyl thiazole hydrazones and their activity against glycation of proteins. Med. Chem., 2015, 24, 3077.
(d) Khan, K.M.; Karim, A.; Ambreen, N.; Saied, S.; Rasheed, S.; Perveen, S.; Choudhary, M.I. Synthesis of benzoxazole derivatives: Antiglycation activity. J. Pharm. Res., 2012, 5, 664.
(e) Khan, K.M.; Badshah, Z.; Ahmad, V.U.; Khan, M.; Taha, M.; Rahim, F.; Jahan, H.; Perveen, S.; Choudhary, M.I. Synthesis of 2,4,6-trichlorophenyl hydrazone and their inhibitory potential against glycation of protein. Med. Chem., 2011, 7, 572.
(f) Khan, K.M.; Rahim, F.; Ambreen, N.; Taha, M.; Khan, M.; Jahan, H.; Najeebullah, S.A.; Iqbal, S.; Perveen, S.; Choudhary, M.I. Synthesis of benzophenone hydrazone Schiff bases and their in vitro antiglycating activities. Med. Chem., 2013, 9, 588.
(g) Khan, K.M.; Khan, M.; Ali, M.; Taha, M.; Rasheed, S.; Perveen, S.; Choudhary, M.I. Synthesis of bis-Schiff bases of isatins and their antiglycation activity. Bioorg. Med. Chem., 2013, 17, 7795.
(h) Khan, K.M.; Mughal, U.R.; Khan, A.; Naz, F.; Perveen, S.; Choudhary, M.I. N-Aroylated isatins: Antiglycation activity. Lett. Drug Des. Discov., 2009, 7, 188.
(i)Khan, K.M.; Mughal, U.R.; Ambreen, N.; Khan, A.; Perveen, S.; Choudhary, M.I. Schiff bases of istain: Antiglycation activity. Lett. Drug Des. Discov., 2009, 6, 358.
(j)Khan, K.M.; Khan, M.; Ambreen, N.; Taha, M.; Rahim, F.; Rasheed, S.; Saied, S.; Safi, H.; Perveen, S.; Choudhary, M.I. Oxindole derivatives: Synthesis and antiglycation activity. Med. Chem., 2013, 9, 681.
kPerveen, S.; Mustafa, S.; Khan, K.M.; Choudhary, M.I. 1,3-Disubstituted ureas as antiglycating agents. J. Chem. Soc. Pak., 2013, 35, 1603.
lKhan, K.M.; Saeed, S.; Ali, M.; Gohar, M.; Zahid, J.; Khan, A.; Perveen, S.; Choudhary, M.I. Unsymmetrically disubstituted urea derivatives: A potent class of antiglycating agents. Bioorg. Med. Chem., 2009, 17, 2447.
mTaha, M.; Ismail, N.H.; Jamil, W.; Rashwan, H.; Kashif, S.M.; Sain, A.A.; Adenan, M.I.; Anouar, E.H.; Rahim, F.; Khan, K.M. Synthesis of novel derivatives of 4-methylbenzimidazole and evaluation of their biological activities. Eur. J. Med. Chem., 2015, 84, 731.
[35]
aSalar, U.; Khan, K.M.; Taha, M.; Ismail, N.H.; Ali, B. Qurat-Ul-Ain; Perveen, S.; Ghufran, M.; Wadood, A. Biology-oriented drug synthesis (BIODS): In vitro β-glucuronidase inhibitory and in silico studies on 2-(2-methyl-5-nitro-1H-imidazol-1-yl)ethyl aryl carboxylate derivatives. Eur. J. Med. Chem., 2017, 125, 1289-1299.
[http://dx.doi.org/10.1016/j.ejmech.2016.11.031] [PMID: 27886546]
b)Ullah, S.; Saeed, M.; Halimi, S.M.A.; Fakhri, M.I.; Khan, K.M.; Khan, I.; Perveen, S. Piroxicam sulfonates biology-oriented drug synthesis (BIODS), characterization and anti-nociceptive screening. Med. Chem. Res., 25, 1468.
[http://dx.doi.org/10.1007/s00044-016-1571-5]
[36]
Vijayalakshmi, K.; Immanuel, S.C.; Sindhu, S.; Arumugam, P. In vitro investigation of antidiabetic potential of selected traditional medicinal plants. Int. J. Pharmacog. Phytochem. Res., 2014, 6, 856.
[37]
Cirillo, V.P. Mechanism of glucose transport across the yeast cell membrane. J. Bacteriol., 1962, 84, 485-491.
[PMID: 14021412]

Rights & Permissions Print Cite
Article Metrics
35
2
1
1
© 2024 Bentham Science Publishers | Privacy Policy