Benzocaine: Review on a Drug with Unfold Potential

Author(s): Syeda Khair-ul-Bariyah, Muhammad Arshad*, Muhammad Ali, Muhammad Imran Din, Ahsan Sharif, Ejaz Ahmed.

Journal Name: Mini-Reviews in Medicinal Chemistry

Volume 20 , Issue 1 , 2020

Become EABM
Become Reviewer

Graphical Abstract:


Abstract:

Benzocaine is well-known for its role as an anesthetic agent and largely used in oral ulcers, ear pain and dental complications. Along with lidocaine and other local anesthetics, benzocaine has marked it as an anesthetic agent in surgical procedures and as Na+ channels blocker, as well. Analogues of benzocaine have been found to possess biological potentials including antibacterial, antifungal and anti-cancer. Some derivatives were found to have conspicuous action against tuberculosis. The current review focuses to explore the century-long potential of the molecule and its analogs that have appeared in the literature. Furthermore, highlighting the biological potential of benzocaine and its analogues shall open-up new dimensions of future research to design more potent analogues.

Keywords: Benzocaine, anesthetic, antibacterial, antifungal, lidocaine, tuberculosis, cancers, antimutagenic.

[1]
Altenburg, A.; El-Haj, N.; Micheli, C.; Puttkammer, M.; Abdel-Naser, M.B.; Zouboulis, C.C. The treatment of chronic recurrent oral aphthous ulcers. Dtsch. Arztebl. Int., 2014, 111(40), 665-673.
[http://dx.doi.org/10.3238/arztebl.2014.0665] [PMID: 25346356]
[2]
Hancock, P.J.; Epstein, J.B.; Sadler, G.R. Oral and dental management related to radiation therapy for head and neck cancer. J. Cancer Dent. Assoc., 2003, 69(9), 585-590.
[PMID: 14653934]
[3]
Hersh, E.V.; Ciancio, S.G.; Kuperstein, A.S.; Stoopler, E.T.; Moore, P.A.; Boynes, S.G.; Levine, S.C.; Casamassimo, P.; Leyva, R.; Mathew, T.; Shibly, O.; Creighton, P.; Jeffers, G.E.; Corby, P.M.A.; Turetzky, S.N.; Papas, A.; Wallen, J.; Idzik-Starr, C.; Gordon, S.M. An evaluation of 10 percent and 20 percent benzocaine gels in patients with acute toothaches: Efficacy, tolerability and compliance with label dose administration directions. J. Am. Dent. Assoc., 2013, 144(5), 517-526.
[http://dx.doi.org/10.14219/jada.archive.2013.0154] [PMID: 23633700]
[4]
Nusstein, J.M.; Beck, M. Effectiveness of 20% benzocaine as a topical anesthetic for intraoral injections. Anesth. Prog., 2003, 50(4), 159-163.
[PMID: 14959903]
[5]
Meechan, J.G. Effective topical anesthetic agents and techniques. Dent. Clin. North Am., 2002, 46(4), 759-766.
[http://dx.doi.org/10.1016/S0011-8532(02)00035-6] [PMID: 12436830]
[6]
Sawchuk, R.J.; Cheung, B.W.Y. Methods and compositions for applying pharmacologic agents to the ear. U.S. Patent 7220431B2, May 22, 2007.
[7]
Al-Samadani, K.H.; Gazal, G. Effectiveness of benzocaine in reducing deep cavity restoration and post-extraction stress in dental patients. Saudi Med. J., 2015, 36(11), 1342-1347.
[http://dx.doi.org/10.15537/smj.2015.11.12274] [PMID: 26593169]
[8]
Rosenfeld, R.M.; Schwartz, S.R.; Cannon, C.R.; Roland, P.S.; Simon, G.R.; Kumar, K.A.; Huang, W.W.; Haskell, H.W.; Robertson, P.J. Clinical practice guideline: Acute otitis externa. Otolaryngol. Head Neck Surg., 2014, 150, S1-S24.
[http://dx.doi.org/10.1177/0194599813514365] [PMID: 24491310]
[9]
Eslamian, L.; Borzabadi-Farahani, A.; Edini, H.Z.; Badiee, M.R.; Lynch, E.; Mortazavi, A. The analgesic effect of benzocaine mucoadhesive patches on orthodontic pain caused by elastomeric separators, a preliminary study. Acta Odontol. Scand., 2013, 71(5), 1168-1173.
[http://dx.doi.org/10.3109/00016357.2012.757358] [PMID: 23301559]
[10]
Li, R.A.; Tsushima, R.G.; Himmeldirk, K.; Dime, D.S.; Backx, P.H. Local anesthetic anchoring to cardiac sodium channels. Implications into tissue-selective drug targeting. Circ. Res., 1999, 85, 88-98.
[http://dx.doi.org/10.1161/01.RES.85.1.88] [PMID: 10400914]
[11]
Omar, R.H.; El-Mouafi, H.R.; Mansour, K. Synthesis of certain 2,4,6-trimethyl-ω-substituted anilides structurally related to anesthetics. ZJPS, 1995, 4(1-B), 200-204.
[12]
Hara, M.; Kai, Y.; Ikemoto, Y. Local anesthetics reduce the inhibitory neurotransmitter-induced current in dissociated hippocampal neurons of the rat. Eur. J. Pharmacol., 1995, 283(1-3), 83-89.
[http://dx.doi.org/10.1016/0014-2999(95)00293-T] [PMID: 7498324]
[13]
Ram, P.S.; Saraswathy, T.; Niraimathi, V.; Indhumathi, B. Synthesis, characterization and antimicrobial activity of some hetero benzocaine derivatives. Int. J. Pharm. Pharm. Sci., 2012, 4(5), 285-287.
[14]
Narayana, B.M.; Lalita, S.; Madhavan, V. Synthesis and antimicrobial activity of some novel pyrrolidine derivatives. Int. J. Chemtech Res., 2012, 4(3), 903-909.
[15]
Kh, Z.A.; Yu, K.M.; Gazaliev, A.M.; Nurkenov, O.A. Synthesis and biological activity of certain derivatives of anesthesine (benzocaine). Russ. J. Gen. Chem., 2008, 78(6), 1253-1254.
[http://dx.doi.org/10.1134/S1070363208060261]
[16]
Uglea, C.V.; Anton, P.; Maria, C.; Dumitriu, A.D.; Ottenbrite, R.M. Distribution and antitumor activity of some carboxymethylcellulose derivatives. Revista de Chimie, 2006, 57(1), 16-20.
[17]
Luminita, P.; Ottenbrite, R.M. Biological effects and antitumor activity induced by benzocaine conjugated anionic polymers. J. Bioact. Compat. Polym., 2002, 17(5), 357-374.
[http://dx.doi.org/10.1177/0883911502017005710]
[18]
Marinov, B.S.; Wang, G.K. Redox properties of local anesthetics: A structural determinant of closed channel blocker in BTX-modified Na+ channels. Biol. Membrany, 2000, 17(4), 438-445.
[19]
Vohra, R.; Huntington, S.; Koike, J.; Le, K.; Geller, R.J. Pediatric exposures to topical benzocaine preparations reported to a statewide poison control system. West. J. Emerg. Med., 2017, 18(5), 923-927.
[http://dx.doi.org/10.5811/westjem.2017.6.33665] [PMID: 28874945]
[20]
Al Nadeesh, F.M.H. Synthesis and Characterization of Several Local Anaesthetics. M.Sc. Thesis, UniversitiTeknologi, Malaysia., 2013.
[21]
Demare, P.; Regla, I. Synthesis of two local anesthetics from toluene: An organic multistep synthesis in a project-oriented laboratory course. J. Chem. Educ., 2012, 89, 147.
[http://dx.doi.org/10.1021/ed100838a]
[22]
Salkowski, H. Ueberesterbildungbeiaromatischenamidosauren. Eur. J. Inorg. Chem., 1895, 28(2), 1917-1923.
[23]
Erlenmeyer, E.; Wanklyn, J.A. Ueber das durchEinwirkung von jodwasserstoff auf mannitbeziehungsweise auf melampyrin (Dulcit) entstehende β hexyljodur und einige seiner derivate. Eur. J. Org. Chem., 1865, 135(2), 129-151.
[24]
Limpricht, H. Ueber die verbindungenausbenzoylchloridoderphtalylchlorid und den estern der dreioxybenzoesauren. Eur. J. Org. Chem., 1898, 303(3), 274-289.
[25]
Adams, R.; Cohen, F.L. Ethyl p-aminobenzoate. Org. Synth., 1928, 8, 66.
[http://dx.doi.org/10.15227/orgsyn.008.0066]
[26]
Ali, S.L. . In: Analytical Profiles of Drug Substances., Ed. Elsevier Science B.V: Amsterdam; 1983, Vol. 12, 73-104.
[27]
Auterhoff, H.; Knabe, J. Lehrbuch der pharmazeutischenChemie, 5th ed; WissenschaftlicheVerlagsgesellschaft Stuttgart: Germany, 1968.
[28]
Ritsert, E. Uber den Werdegang des Anasthesins. Pharm. Ztg., 1925, 60, 1006-1008.
[29]
Lide, D.R. CRC Handbook of Chemistry and Physics, 81st ed; CRC Press: Florida, 2000.
[30]
Pavia, D.L.; Lampman, G.M.; Kriz, G.S.; Engel, R.G. A small-scale approach to organic laboratory techniques, 3rd ed; Brooks/Cole: United States, 1989.
[31]
Susan, B. The Merck Index - an encyclopedia of chemicals, drugs, and biological., 13th ed.; Whitehouse Station: New Jersey. 2001
[32]
Lide, D.R.; Milne, G.W.A. Handbook of Data on Organic Compounds, 3rd ed; CRC Press: Florida, 1995.
[33]
Yalkowsky, S.H.; He, Y.; Jain, P. Handbook of aqueous solubility data, 2nd ed; CRC Press: Florida, 2010.
[34]
Thomson, P.D.R.; Montvale, N.J. Physicians Desk Reference., 2004, 58, 1130.
[35]
Jiwa, N.; Ibe, U.; Beri, R. Benzocaine spray-induced methemoglobinemia. Am. J. Respir. Crit. Care Med., 2018, 197, A6587.
[36]
Liebelt, E.L.; Shannon, M.W. Small doses, big problems: A selected review of highly toxic common medications. Pediatr. Emerg. Care, 1993, 9(5), 292-297.
[http://dx.doi.org/10.1097/00006565-199310000-00008] [PMID: 8247936]
[37]
Veltri, K.T.; Rudnick, E. Benzocaine-induced methemoglobinemia: A case report. P&T, 2016, 41(3), 180-191.
[PMID: 26957886]
[38]
Shua-Haim, J.R.; Gross, J.S. Methemoglobinemia toxicity from topical benzocaine spray. J. Am. Geriatr. Soc., 1995, 43(5), 590.
[http://dx.doi.org/10.1111/j.1532-5415.1995.tb06117.x] [PMID: 7730550]
[39]
Sidhu, S.K.; Shaw, S.; Wilkinson, J.D. A 10-year retrospective study on benzocaine allergy in the United Kingdom. Am. J. Contact Dermat., 1999, 10(2), 57-61.
[http://dx.doi.org/10.1016/S1046-199X(99)90000-3] [PMID: 10357712]
[40]
González-Rodríguez, A.J.; Gutiérrez-Paredes, E.M.; Revert Fernández, Á.; Jordá-Cuevas, E. Allergic contact dermatitis to benzocaine: The importance of concomitant positive patch test results. Actas Dermosifiliogr., 2013, 104(2), 156-158.
[http://dx.doi.org/10.1016/j.adengl.2011.07.011] [PMID: 22551703]
[41]
Vu, A.T.; Lockey, R.F. Benzocaine anaphylaxis. J. Allergy Clin. Immunol., 2006, 118(2), 534-535.
[http://dx.doi.org/10.1016/j.jaci.2006.04.035] [PMID: 16890789]
[42]
Rodriguez, L.F.; Smolik, L.M.; Zbehlik, A.J. Benzocaine-induced methemoglobinemia: Report of a severe reaction and review of the literature. Ann. Pharmacother., 1994, 28(5), 643-649.
[http://dx.doi.org/10.1177/106002809402800515] [PMID: 8069004]
[43]
Johansen, F.A. Benzocaine-chaulmoogra oil in the treatment of leprosy. Public Health Rep., 1927, 42(49), 3005-3059.
[http://dx.doi.org/10.2307/4578607] [PMID: 19315116]
[44]
Bray, G.W. An Address on the treatment of allergic diseases in general practice. BMJ, 1933, 2(3783), 43-47.
[http://dx.doi.org/10.1136/bmj.2.3783.43] [PMID: 20777642]
[45]
Stevenson, R.S. Quinsy and retropharyngeal abscess. BMJ, 1938, 1(4041), 1323-1325.
[http://dx.doi.org/10.1136/bmj.1.4041.1323] [PMID: 20781539]
[46]
Hamblen-Thomas, C. Factors in painless tonsillectomy. Postgrad. Med. J., 1938, 14(151), 147-150.
[http://dx.doi.org/10.1136/pgmj.14.151.147] [PMID: 21313113]
[47]
Carpenter, C.C.; Heinlein, J.A.; Sulzberger, M.B.; Baer, R.L. Scabies and pediculosis treated with benzyl benzoate, DDT benzocaine emulsion, including a comparison with other methods used at the U.S.N. hospital, Brooklyn, N. Y. J. Invest. Dermatol., 1946, 7, 93-98.
[http://dx.doi.org/10.1038/jid.1946.8]
[48]
Belinkoff, S. Prolonged intercostal nerve block in upper abdominal operations. Ann. Surg., 1948, 127, 136-143.
[http://dx.doi.org/10.1097/00000658-194801000-00013] [PMID: 17859055]
[49]
Russell, W.R.; Spalding, J.M.K. Treatment of painful amputation stumps. BMJ, 1950, 2(4670), 68-73.
[http://dx.doi.org/10.1136/bmj.2.4670.68] [PMID: 15426811]
[50]
Kohn, J.; Rutter, A.G.; Vitali, M. Prolonged local analgesia with benzocaine-urethane solution. BMJ, 1954, 2(4889), 682-684.
[http://dx.doi.org/10.1136/bmj.2.4889.682] [PMID: 13190229]
[51]
Graham, P.A. Benzocaine-urethane solution in ophthalmology. Br. J. Ophthalmol., 1958, 42(10), 589-594.
[http://dx.doi.org/10.1136/bjo.42.10.589] [PMID: 13584708]
[52]
Dubow, E. A new ceruminolytic for use in pediatric ear examinations. AMA J. Dis. Child., 1959, 97(6), 863-864.
[PMID: 13649121]
[53]
Savvidi, G.L. The efficiency of anesthesia with lidocaine, procaine and benzocaine in tooth preparation for fixed prosthesis. Stomatologiia., 1968, 47(4), 51-53.
[54]
Felder, S.M.; Farrell, C.D.; Koerker, R.L. Methylcellulose as a vehicle for topical anesthetics. Anesth. Prog., 1977, 24(4), 112-117.
[PMID: 333992]
[55]
Hille, B. The pH-dependent rate of action of local anesthetics on the node of Ranvier. J. Gen. Physiol., 1977, 69(4), 475-496.
[http://dx.doi.org/10.1085/jgp.69.4.475] [PMID: 16078]
[56]
Chipley, J.R.; Uraih, N. Inhibition of Aspergillus growth and aflatoxin release by derivatives of benzoic acid. Appl. Environ. Microbiol., 1980, 40(2), 352-357.
[PMID: 6781406]
[57]
Huang, L.M.; Ehrenstein, G. Local anesthetics QX 572 and benzocaine act at separate sites on the batrachotoxin-activated sodium channel. J. Gen. Physiol., 1981, 77(2), 137-153.
[http://dx.doi.org/10.1085/jgp.77.2.137] [PMID: 6267160]
[58]
Schneider, M.F.; Dubois, J.M. Effects of benzocaine on the kinetics of normal and batrachotoxin-modified Na channels in frog node of Ranvier. Biophys. J., 1986, 50(3), 523-530.
[http://dx.doi.org/10.1016/S0006-3495(86)83490-7] [PMID: 2428413]
[59]
Morrow, M.E.; Berry, C.W. Antimicrobial properties of topical anesthetic liquids containing lidocaine or benzocaine. Anesth. Prog., 1988, 35(1), 9-13.
[PMID: 3278655]
[60]
Claude, B.J.; Claude, S.J.; Florence, C. Polymerization of vinyl chloroformate derivatives, 2. Vinyl carbamate of benzocaine. Makromol. Chem., Rapid. Commun., 1985, 6(8), 567-571.
[http://dx.doi.org/10.1002/marc.1985.030060810]
[61]
Bradley, D.J.; Richards, C.D. Temperature-dependence of the action of nerve blocking agents and its relationship to membrane-buffer partition coefficients: Thermodynamic implications for the site of action of local anaesthetics. Br. J. Pharmacol., 1984, 81, 161-167.
[http://dx.doi.org/10.1111/j.1476-5381.1984.tb10756.x] [PMID: 6704579]
[62]
Hishinuma, S.; Uchida, M.K. Effects of local anaesthetics on short-term desensitization of guinea-pig taenia caecum to histamine. Br. J. Pharmacol., 1987, 92(4), 733-741.
[http://dx.doi.org/10.1111/j.1476-5381.1987.tb11377.x] [PMID: 3427278]
[63]
Zheng, Y. Antitumor compounds. II. Synthesis of derivatives of some plant growth regulators (analogs of benzocaine). ZhongshanDaxueXuebaoZiranKexue Ban., 1986, 4, 109-111.
[64]
Parekh, B.R.; Patel, J.M.; Thaker, K.A. Studies on 1,3,5-triazines: Preparation of 2-arylamino-4-(4-carboxy-3-hydroxyanilino)-6-(4-carbethoxyanilino)-1,3,5-triazine. J. Inst. Chem.(India), 1987, 59(5), 237-238.
[65]
Gangarosa, L.P., Sr; Ciarlone, A.E.; Neaverth, E.J.; Johnston, C.A.; Snowden, J.D.; Thompson, W.O. Use of verbal descriptors, thermal scores and electrical pulp testing as predictors of tooth pain before and after application of benzocaine gels into cavities of teeth with pulpitis. Anesth. Prog., 1989, 36(6), 272-275.
[PMID: 2490060]
[66]
Rosivack, R.G.; Koenigsberg, S.R.; Maxwell, K.C. An analysis of the effectiveness of two topical anesthetics. Anesth. Prog., 1990, 37(6), 290-292.
[PMID: 2097909]
[67]
Serge, R.; Maryse, G.; Alain, R. Preparation and activity of controlled- action anesthetic compounds and pharmaceutical compositions containing benzocaine. U.S. Patent WO9011292, October 4. 1990
[68]
Uglea, C.V.; Albu, I.N.; Vatajanu, A.; Croitoru, M.; Polyanionicpolymers, I. Synthesis, characterization and potential medical applications of benzocaine modified carboxymethylcellulose. J. Bioact. Compat. Polym., 1994, 9, 448-461.
[http://dx.doi.org/10.1177/088391159400900406]
[69]
Bronaugh, R.L.; Collier, S.W.; Macpherson, S.E.; Kraeling, M.E. Influence of metabolism in skin on dosimetry after topical exposure. Environ. Health Perspect., 1994, 102(Suppl. 11), 71-74.
[http://dx.doi.org/10.1289/ehp.94102s1171] [PMID: 7737045]
[70]
Lambert, C.; Erdmann, A.; Eikmanns, M.; Kramer, R. Triggering glutamate excretion in Corynebacterium glutamicum by modulating the membrane state with local anesthetics and osmotic gradients. Appl. Environ. Microbiol., 1995, 61(12), 4334-4342.
[PMID: 16535186]
[71]
Quan, C.; Mok, W.M.; Wang, G.K. Use-dependent inhibition of Na+ currents by benzocaine homologs. Biophys. J., 1996, 70, 194-201.
[http://dx.doi.org/10.1016/S0006-3495(96)79563-2] [PMID: 8770198]
[72]
Dear, J.W.; Ghali, S.; Foreman, J.C. Attenuation of human nasal airway responses to bradykinin and histamine by inhibitors of nitric oxide synthase. Br. J. Pharmacol., 1996, 118(5), 1177-1182.
[http://dx.doi.org/10.1111/j.1476-5381.1996.tb15521.x] [PMID: 8818341]
[73]
Pathan, M.D.; Khunt, R.C.; Datta, N.J.; Parikh, A.R. 2-Aryl-3-(2′-p-chlorophenyl-1′,3′,4′-oxadiazol-5′-ylphenyl)-4-thiazolidinones. J. Inst. Chem.(India), 2000, 72(5), 190-191.
[74]
Khazaei, A.; Zolfigol, M.A.; Abedian, N. A novel synthesis and characterization of poly[4-imino(N-4-ethylbenzoate)benzene p-styrenesulphonate] and the investigation on polymer ability for drug release. Iran. Polym. J., 2001, 10, 59-65.
[75]
Chidambaram, N.; Burgess, D.J. Effect of nonionic surfactant on transport of surface-active and non-surface-active model drugs and emulsion stability in triphasic systems. AAPS PharmSci, 2000, 2(3)E30
[http://dx.doi.org/10.1208/ps020330] [PMID: 11741246]
[76]
Chidambaram, N.; Burgess, D.J. Mathematical modeling of surface-active and non-surface-active drug transport in emulsion systems. AAPS PharmSci, 2000, 2(3) E31
[http://dx.doi.org/10.1208/ps020331] [PMID: 11741247]
[77]
Hollmann, M.W.; Ritter, C.H.; Henle, P.; de Klaver, M.; Kamatchi, G.L.; Durieux, M.E. Inhibition of m3 muscarinic acetylcholine receptors by local anaesthetics. Br. J. Pharmacol., 2001, 133, 207-216.
[http://dx.doi.org/10.1038/sj.bjp.0704040] [PMID: 11325812]
[78]
Dash, A.K.; Cudworth, G.C., II Evaluation of an acetic acid ester of monoglyceride as a suppository base with unique properties. AAPS PharmSciTech, 2001, 2(3) E13
[http://dx.doi.org/10.1208/pt020313] [PMID: 14727872]
[79]
Panaitescu, L.; Ottenbrite, R.M. Biological effects and antitumor activity induced by benzocaine conjugated anionic polymers. J. Bioact. Compat. Polym., 2002, 17, 357-374.
[http://dx.doi.org/10.1177/0883911502017005710]
[80]
Sachdeva, R.; Pugeda, J.G.; Casale, L.R.; Meizlish, J.L.; Zarich, S.W. Benzocaine-induced methemoglobinemia: A potentially fatal complication of transesophageal echocardiography. Tex. Heart Inst. J., 2003, 30(4), 308-310.
[PMID: 14677742]
[81]
Chander, K.; Lavie, C.J.; Ventura, H.O.; Milani, R.V. Benzocaine induced methemoglobinemia: A potentially fatal complication of transesophageal echocardiography. Ochsner J., 2003, 5(2), 34-35.
[PMID: 22826681]
[82]
Hegedus, F.; Herb, K. Benzocaine-induced methemoglobinemia. Anesth. Prog., 2005, 52(4), 136-139.,
[http://dx.doi.org/10.2344/0003-3006(2005)52[136:BM]2.0.CO;2] [PMID: 16596913]
[83]
Kamel, M.M.; Nofal, Z.M.; Zaghary, W.A.; Refai, M.; Ismail, N.S. Synthesis of some new 4-(p-heterocyclo-substituted anilino) -2,7-dimethyl-1,8-naphthyridines of expected antimicrobial activity. E-J. Chem., 2007, 50(3), 369-390.
[84]
Pejin, B.; Iodice, C.; Tommonaro, G.; De Rosa, S. Synthesis and biological activities of thio-avarol derivatives. J. Nat. Prod., 2008, 71(11), 1850-1853.
[http://dx.doi.org/10.1021/np800318m] [PMID: 19007183]
[85]
Tantisattamo, E.; Suwantarat, N.; Vierra, J.R.; Evans, S.J. Atypical presentations of methemoglobinemia from benzocaine spray. Hawaii Med. J., 2011, 70(6), 125-126.
[PMID: 22162610]
[86]
Lee, S.; Goodchild, S.J.; Ahern, C.A. Local anesthetic inhibition of a bacterial sodium channel. J. Gen. Physiol., 2012, 139(6), 507-516.
[http://dx.doi.org/10.1085/jgp.201210779] [PMID: 22641643]
[87]
Chaturvedi, P.; Valentina, P.; Kamaria, P. Synthesis, characterization and biological evaluation of some novel condensed 3,6-disubstituted-1,2,4-triazolo-1,3,4-thiadiazole derivatives. Der Pharm. Lett., 2013, 5(4), 344-350.
[88]
Gavat, C.C.; Uglea, C.V.; Valerica, G.C. Biological activity of the oxidized polysaccharides. Rev. Roum. Chim., 2013, 58(6), 479-489.
[89]
Martin, L.J.; Corry, B. Locating the route of entry and binding sites of benzocaine and phenytoin in a bacterial voltage gated sodium channel. PLOS Comput. Biol., 2014, 10(7) e1003688
[http://dx.doi.org/10.1371/journal.pcbi.1003688] [PMID: 24992293]
[90]
Mehta, P.; Chovatiya, P.; Joshi, H.S. Synthesis, characterization and antimicrobial evaluation of some novel benzenesulfonylhydrazone derivatives of benzimidazole. Der ChemicaSinica., 2015, 6(2), 29-34.
[91]
Jun, T.; Yu, S.; Lingling, L.; Zhen, X.; Zaosheng, L. Research on synthesis of new azo calyx[4]arene and its dyeing properties. MATEC Web. Conf., 2015. 2015
[92]
Paluch, A.S.; Parameswaran, S.; Liu, S.; Kolavennu, A.; Mobley, D.L. Predicting the excess solubility of acetanilide, acetaminophen, phenacetin, benzocaine, and caffeine in binary water/ethanol mixtures via molecular simulation. J. Chem. Phys., 2015, 142(4) 044508
[http://dx.doi.org/10.1063/1.4906491] [PMID: 25637996]
[93]
Kumar, P.M.R.; Joshi, S.D.; Dixit, S.R.; Kulkarni, V.H. Synthesis, antibacterial and antitubercular activities of novel N1-[2-(substituted phenylamino)acetyl]-4-(1Hpyrrol-1-yl)-benzohydrazide derivatives. Indian J. Heterocycl. Chem., 2015, 25, 37-44.
[94]
Tommonaro, G.; García-Font, N.; Vitale, R.M.; Pejin, B.; Iodice, C.; Cañadas, S.; Marco-Contelles, J.; Oset-Gasque, M.J. Avarol derivatives as competitive AChE inhibitors, non hepatotoxic and neuroprotective agents for Alzheimer’s disease. Eur. J. Med. Chem., 2016, 122(122), 326-338.
[http://dx.doi.org/10.1016/j.ejmech.2016.06.036] [PMID: 27376495]
[95]
Ling, J.; Kavuru, P.; Wojtas, L.; Chadwick, K. Crystal structure of ethyl 4-[(E)-(4-hy-droxy-3-meth-oxy-benzyl-idene)amino]-benzoate: A p-hy-droxy Schiff base. Acta Crystallogr. E Crystallogr. Commun., 2016, 72(Pt 7), 951-954.
[http://dx.doi.org/10.1107/S2056989016008999] [PMID: 27555938]
[96]
Gouhar, R.S.; Usama, F.; El-Shehry, M.F.; El-Hallouty, S.M. Synthesis and anticancer evaluation of some new polyfunctionally substituted pyrimidine derivatives. Pharma Chem., 2016, 8(15), 134-145.
[97]
Skår, M.W.; Haugland, G.T.; Powell, M.D.; Wergeland, H.I.; Samuelsen, O.B. Development of anaesthetic protocols for lumpfish (Cyclopterus lumpus L.): Effect of anaesthetic concentrations, sea water temperature and body weight. PLoS One, 2017, 12(7) e0179344
[http://dx.doi.org/10.1371/journal.pone.0179344] [PMID: 28678815]
[98]
Ihsan, H.M.; Guler, G.; Temel, Y.; Sadik, K.; Guniz, K.S. Synthesis and antibacterial activity of new hydrazide-hydrazones derived from benzocaine. Marmara Pharm. J., 2017, 21(4), 961-966.
[http://dx.doi.org/10.12991/mpj.2017.34]
[99]
Holbrook, A.; Wright, M.; Sung, M.; Ribic, C.; Baker, S. Statin-associated rhabdomyolysis: Is there a dose-response relationship? Can. J. Cardiol., 2011, 27(2), 146-151.
[http://dx.doi.org/10.1016/j.cjca.2010.12.024] [PMID: 21459261]
[100]
Fernandes, J.P.S. The importance of medicinal chemistry knowledge in the clinical pharmacist’s education. Am. J. Pharm. Educ., 2018, 82(2), 6083.
[http://dx.doi.org/10.5688/ajpe6083] [PMID: 29606703]


Rights & PermissionsPrintExport Cite as


Article Details

VOLUME: 20
ISSUE: 1
Year: 2020
Page: [3 - 11]
Pages: 9
DOI: 10.2174/1389557519666190913145423
Price: $65

Article Metrics

PDF: 28
HTML: 3
EPUB: 1
PRC: 1