In vitro Inhibition Profiles and Molecular Docking Analysis of Benzohydrazide
Derivatives on Red Blood Cell Carbonic Anhydrases Isozymes

Işıl   Nihan   Korkmaz; Pınar      Güller; Ramazan      Kalın; Aykut      Öztekin; Hasan      Özdemir

doi:10.2174/1573409918666220818114505

Abstract

Background: Carbonic anhydrases (CAs, EC 4.2.1.1) are metalloenzymes that contain zinc ions on the active side and convert carbon dioxide to bicarbonate in metabolism. Human CA-I and CA-II, which are the most abundant CA isozymes in erythrocytes, have been therapeutic targets in the treatment of glaucoma, hypertension, ulcer, osteoporosis, and, neurological disorders. Benzohydrazides are biologically active compounds, and their various pharmacological effects have been reported.

Aim: In light of this, the objective of this study was to investigate the in vitro effects of benzohydrazide derivatives on the activities of hCA-I and hCA-II, determine the compounds as selective inhibitors for these isoenzymes, and estimate the inhibition mechanism through molecular docking studies.

Methods: In this work, we synthesized the 10 different derivatives of benzohydrazide containing various functional group of different positions.

Results: As a result, all benzohydrazide derivatives inhibited both isozymes in vitro and 2-amino 3- nitro benzohydrazide (10) was found to be the most efficient inhibitor of both hCA isozymes with the IC₅₀ values of 0.030 and 0.047 μM, respectively. In the molecular docking studies, 3-amino 2- methyl benzohydrazide (3) had the lowest estimated free binding energies against hCA isozymes as -6.43 and -6.13 kcal/mol.

Conclusion: In this study, hCA-I & II isozymes were isolate from human erythrocytes. CA isozymes are one of these target enzymes. WBC hope that the benzohydrazide derivatives, can guide remedies targeting carbonic anhydrase.

Keywords: Carbonic anhydrase, drug-likeness, structure-activity relationship, inhibition, molecular docking, isozymes.

« Previous Next »

Graphical Abstract

[1]
Aggarwal, M.; McKenna, R. Update on carbonic anhydrase inhibitors: A patent review (2008 - 2011). Expert Opin. Ther. Pat.,  2012, 22(8), 903-915.
 [http://dx.doi.org/10.1517/13543776.2012.707646] [PMID: 22788994]

[2]
Alterio, V.; Di Fiore, A.; D’Ambrosio, K.; Supuran, C.T.; De Simone, G. Multiple binding modes of inhibitors to carbonic anhydrases: How to design specific drugs targeting 15 different isoforms? Chem. Rev.,  2012, 112(8), 4421-4468.
 [http://dx.doi.org/10.1021/cr200176r] [PMID: 22607219]

[3]
Supuran, C.T. Carbonic anhydrases: Novel therapeutic applications for inhibitors and activators. Nat. Rev. Drug Discov.,  2008, 7(2), 168-181.
 [http://dx.doi.org/10.1038/nrd2467] [PMID: 18167490]

[4]
Supuran, C.T.; Scozzafava, A. Carbonic anhydrases as targets for medicinal chemistry. Bioorg. Med. Chem.,  2007, 15(13), 4336-4350.
 [http://dx.doi.org/10.1016/j.bmc.2007.04.020] [PMID: 17475500]

[5]
Supuran, C.T. Structure-based drug discovery of carbonic anhydrase inhibitors. J. Enzyme Inhib. Med. Chem.,  2012, 27(6), 759-772.
 [http://dx.doi.org/10.3109/14756366.2012.672983] [PMID: 22468747]

[6]
Karhumaa, P.; Leinonen, J.; Parkkila, S.; Kaunisto, K.; Tapanainen, J.; Rajaniemi, H. The identification of secreted carbonic anhydrase VI as a constitutive glycoprotein of human and rat milk. Proc. Natl. Acad. Sci. USA,  2001, 98(20), 11604-11608.
 [http://dx.doi.org/10.1073/pnas.121172598] [PMID: 11553764]

[7]
Maren, T.H. The kinetics of HCO3- synthesis related to fluid secretion, pH control, and CO2 elimination. Annu. Rev. Physiol.,  1988, 50(1), 695-717.
 [http://dx.doi.org/10.1146/annurev.ph.50.030188.003403] [PMID: 3132082]

[8]
Chang, X.; Zheng, Y.; Yang, Q.; Wang, L.; Pan, J.; Xia, Y.; Yan, X.; Han, J. Carbonic anhydrase I (CA1) is involved in the process of bone formation and is susceptible to ankylosing spondylitis. Arthritis Res. Ther.,  2012, 14(4), R176.
 [http://dx.doi.org/10.1186/ar3929] [PMID: 22838845]

[9]
Zheng, Y.; Wang, L.; Zhang, W.; Xu, H.; Chang, X. Transgenic mice over-expressing carbonic anhydrase I showed aggravated joint inflammation and tissue destruction. BMC Musculoskelet. Disord.,  2012, 13(1), 256.
 [http://dx.doi.org/10.1186/1471-2474-13-256] [PMID: 23256642]

[10]
Zheng, Y.; Xu, B.; Zhao, Y.; Gu, H.; Li, C.; Wang, Y.; Chang, X. CA1 contributes to microcalcification and tumourigenesis in breast cancer. BMC Cancer,  2015, 15(1), 679.
 [http://dx.doi.org/10.1186/s12885-015-1707-x] [PMID: 26459317]

[11]
Altıntop, M.D.; Sever, B.; Akalın Çiftçi, G.; Kucukoglu, K.; Özdemir, A.; Soleimani, S.S.; Nadaroglu, H.; Kaplancıklı, Z.A. Synthesis and evaluation of new benzodioxole-based dithiocarbamate derivatives as potential anticancer agents and hCA-I and hCA-II inhibitors. Eur. J. Med. Chem.,  2017, 125, 190-196.
 [http://dx.doi.org/10.1016/j.ejmech.2016.09.035] [PMID: 27657811]

[12]
Frazier, M.L.; Lilly, B.J.; Wu, E.F.; Ota, T.; Hewett-Emmett, D. Carbonic anhydrase II gene expression in cell lines from human pancreatic adenocarcinoma. Pancreas,  1990, 5(5), 507-514.
 [http://dx.doi.org/10.1097/00006676-199009000-00002] [PMID: 1700414]

[13]
Parkkila, A-K.; Herva, R.; Parkkila, S.; Rajaniemi, H. Immunohistochemical demonstration of human carbonic anhydrase isoenzyme II in brain tumours. Histochem. J.,  1995, 27(12), 974-982.
 [http://dx.doi.org/10.1007/BF02389687] [PMID: 8789398]

[14]
Parkkila, S.; Rajaniemi, H.; Parkkila, A-K.; Kivelä, J.; Waheed, A.; Pastoreková, S.; Pastorek, J.; Sly, W.S. Carbonic anhydrase inhibitor suppresses invasion of renal cancer cells in vitro. Proc. Natl. Acad. Sci. USA,  2000, 97(5), 2220-2224.
 [http://dx.doi.org/10.1073/pnas.040554897] [PMID: 10688890]

[15]
Pastoreková, S.; Parkkila, S.; Parkkila, A.K.; Opavský, R.; Zelník, V.; Saarnio, J.; Pastorek, J. Carbonic anhydrase IX, MN/CA IX: Analysis of stomach complementary DNA sequence and expression in human and rat alimentary tracts. Gastroenterology,  1997, 112(2), 398-408.
 [http://dx.doi.org/10.1053/gast.1997.v112.pm9024293] [PMID: 9024293]

[16]
Lomelino, C.L.; Supuran, C.T.; McKenna, R. Non-classical inhibition of carbonic anhydrase. Int. J. Mol. Sci.,  2016, 17(7), 1150.
 [http://dx.doi.org/10.3390/ijms17071150] [PMID: 27438828]

[17]
Hermanson, G.T. Bioconjugate Techniques; Academic Press: San Diego, 2013. 

[18]
Supuran, C.T. Carbonic anhydrases as drug targets--an overview. Curr. Top. Med. Chem.,  2007, 7(9), 825-833.
 [http://dx.doi.org/10.2174/156802607780636690] [PMID: 17504127]

[19]
Jensen, E.L.; Clement, R.; Kosta, A.; Maberly, S.C.; Gontero, B. A new widespread subclass of carbonic anhydrase in marine phytoplankton. ISME J.,  2019, 13(8), 2094-2106.
 [http://dx.doi.org/10.1038/s41396-019-0426-8] [PMID: 31024153]

[20]
Kalaycı, M.; Türkeş, C.; Arslan, M.; Demir, Y.; Beydemir, Ş. Novel benzoic acid derivatives: Synthesis and biological evaluation as multitarget acetylcholinesterase and carbonic anhydrase inhibitors. Arch. Pharm. (Weinheim),  2021, 354(3), e2000282.
 [http://dx.doi.org/10.1002/ardp.202000282] [PMID: 33155700]

[21]
Sever, B.; Türkeş, C.; Altıntop, M.D.; Demir, Y.; Beydemir, Ş. Thiazolyl-pyrazoline derivatives: In vitro and in silico evaluation as potential acetylcholinesterase and carbonic anhydrase inhibitors. Int. J. Biol. Macromol.,  2020, 163, 1970-1988.
 [http://dx.doi.org/10.1016/j.ijbiomac.2020.09.043] [PMID: 32931834]

[22]
Almaz, Z.; Oztekin, A.; Abul, N.; Gerni, S.; Erel, D.; Kocak, S.M.; Sengül, M.E.; Ozdemir, H. A new approach for affinity-based purification of horseradish peroxidase. Biotechnol. Appl. Biochem.,  2021, 68(1), 102-113.
 [http://dx.doi.org/10.1002/bab.1899] [PMID: 32060967]

[23]
Oztekin, A.; Almaz, Z.; Gerni, S.; Erel, D.; Kocak, S.M.; Sengül, M.E.; Ozdemir, H. Purification of peroxidase enzyme from radish species in fast and high yield with affinity chromatography technique. J. Chromatogr. B Analyt. Technol. Biomed. Life Sci.,  2019, 1114-1115, 86-92.
 [http://dx.doi.org/10.1016/j.jchromb.2019.03.035] [PMID: 30939412]

[24]
Yamada, H.; Kojo, M.; Nakahara, T.; Murakami, K.; Kakima, T.; Ichiba, H.; Yajima, T.; Fukushima, T. Development of a fluorescent chelating ligand for scandium ion having a Schiff base moiety. Spectrochim. Acta A Mol. Biomol. Spectrosc.,  2012, 90, 72-77.
 [http://dx.doi.org/10.1016/j.saa.2012.01.014] [PMID: 22316617]

[25]
Nalbantoğlu, B.; Demir, N.; Özdemir, H.; Küfrevioğlu, Ö.İ. A new method for the purification of carbonic anhydrase isozymes by affinity chromatography. Turk. J. Med. Sci.,  1996, 26(2), 163-166.

[26]
Bradford, M.M. A rapid and sensitive method for the quantitation of microgram quantities of protein utilizing the principle of protein-dye binding. Anal. Biochem.,  1976, 72(1-2), 248-254.
 [http://dx.doi.org/10.1016/0003-2697(76)90527-3] [PMID: 942051]

[27]
Verpoorte, J.A.; Mehta, S.; Edsall, J.T. Esterase activities of human carbonic anhydrases B and C. J. Biol. Chem.,  1967, 242(18), 4221-4229.
 [http://dx.doi.org/10.1016/S0021-9258(18)95800-X] [PMID: 4964830]

[28]
Lineweaver, H.; Burk, D. The determination of enzyme dissociation constants. J. Am. Chem. Soc.,  1934, 56(3), 658-666.
 [http://dx.doi.org/10.1021/ja01318a036]

[29]
Daina, A.; Michielin, O.; Zoete, V. SwissADME: A free web tool to evaluate pharmacokinetics, drug-likeness and medicinal chemistry friendliness of small molecules. Sci. Rep.,  2017, 7(1), 42717.
 [http://dx.doi.org/10.1038/srep42717] [PMID: 28256516]

[30]
Pires, D.E.; Blundell, T.L.; Ascher, D.B. PkCSM: Predicting small-molecule pharmacokinetic and properties using graph-based signatures. J. Med. Chem.,  2015, 58, 4066-4072.
 [http://dx.doi.org/10.1021/acs.jmedchem.5b00104]

[31]
Tian, W.; Chen, C.; Lei, X.; Zhao, J.; Liang, J. CASTp 3.0: Computed atlas of surface topography of proteins. Nucleic Acids Res.,  2018, 46(W1), W363-W367.
 [http://dx.doi.org/10.1093/nar/gky473] [PMID: 29860391]

[32]
Morris, G.M.; Huey, R.; Lindstrom, W.; Sanner, M.F.; Belew, R.K.; Goodsell, D.S.; Olson, A.J. AutoDock4 and AutoDockTools4: Automated docking with selective receptor flexibility. J. Comput. Chem.,  2009, 30(16), 2785-2791.
 [http://dx.doi.org/10.1002/jcc.21256] [PMID: 19399780]

[33]
Alterio, V.; Monti, S.M.; Truppo, E.; Pedone, C.; Supuran, C.T.; De Simone, G. The first example of a significant active site conformational rearrangement in a carbonic anhydrase-inhibitor adduct: The carbonic anhydrase I-topiramate complex. Org. Biomol. Chem.,  2010, 8(15), 3528-3533.
 [http://dx.doi.org/10.1039/b926832d] [PMID: 20505865]

[34]
Ivanova, J.; Leitans, J.; Tanc, M.; Kazaks, A.; Zalubovskis, R.; Supuran, C.T.; Tars, K. X-ray crystallography-promoted drug design of carbonic anhydrase inhibitors. Chem. Commun. (Camb.),  2015, 51(33), 7108-7111.
 [http://dx.doi.org/10.1039/C5CC01854D] [PMID: 25813715]

[35]
Shivanika, C.; Kumar, D.; Ragunathan, V.; Tiwari, P.; Sumitha, A. Molecular docking, validation, dynamics simulations, and pharmacokinetic prediction of natural compounds against the SARS-CoV-2 main-protease. J. Biomol. Struct. Dyn.,  2022, 40(2), 585-611.
 [PMID: 32897178]

[36]
Güller, P.; Dağalan, Z.; Güller, U.; Çalışır, U.; Nişancı, B. Enzymes inhibition profiles and antibacterial activities of benzylidenemalononitrile derivatives. J. Mol. Struct.,  2021, 1239, 130498.
 [http://dx.doi.org/10.1016/j.molstruc.2021.130498]

[37]
Nocentini, A.; Supuran, C.T. Carbonic anhydrase inhibitors as antitumor/antimetastatic agents: A patent review (2008-2018). Expert Opin. Ther. Pat.,  2018, 28(10), 729-740.
 [http://dx.doi.org/10.1080/13543776.2018.1508453] [PMID: 30074415]

[38]
Pastorekova, S.; Casini, A.; Scozzafava, A.; Vullo, D.; Pastorek, J.; Supuran, C.T. Carbonic anhydrase inhibitors: The first selective, membrane-impermeant inhibitors targeting the tumor-associated isozyme IX. Bioorg. Med. Chem. Lett.,  2004, 14(4), 869-873.
 [http://dx.doi.org/10.1016/j.bmcl.2003.12.029] [PMID: 15012984]

[39]
Supuran, C.T. Carbonic anhydrase inhibitors. Bioorg. Med. Chem. Lett.,  2010, 20(12), 3467-3474.
 [http://dx.doi.org/10.1016/j.bmcl.2010.05.009] [PMID: 20529676]

[40]
Supuran, C.T.; Scozzafava, A. Carbonic anhydrase inhibitors and their therapeutic potential. Expert Opin. Ther. Pat.,  2000, 10(5), 575-600.
 [http://dx.doi.org/10.1517/13543776.10.5.575] [PMID: 30217119]

[41]
Narang, R.; Narasimhan, B.; Sharma, S. A review on biological activities and chemical synthesis of hydrazide derivatives. Curr. Med. Chem.,  2012, 19(4), 569-612.
 [http://dx.doi.org/10.2174/092986712798918789] [PMID: 22204327]

[42]
Saini, M.; Kumar, P.; Kumar, M.; Ramasamy, K.; Mani, V.; Mishra, R.K.; Majeed, A.B.A.; Narasimhan, B. Synthesis, in vitro antimicrobial, anticancer evaluation and QSAR studies of N′-(substituted)-4-(butan-2-lideneamino) benzohydrazides. Arab. J. Chem.,  2014, 7(4), 448-460.
 [http://dx.doi.org/10.1016/j.arabjc.2013.05.010]

[43]
Al-Abdullah, E.S. Synthesis and anticancer activity of some novel tetralin-6-yl-pyrazoline, 2-thioxopyrimidine, 2-oxopyridine, 2-thioxo-pyridine and 2-iminopyridine derivatives. Molecules,  2011, 16(4), 3410-3419.
 [http://dx.doi.org/10.3390/molecules16043410] [PMID: 21512449]

[44]
Mohareb, R.M.; Mohamed, A.A. The reaction of cyanoacetylhydrazine with ω-bromo(4-methyl)acetophenone: Synthesis of heterocyclic derivatives with antitumor activity. Molecules,  2010, 15(5), 3602-3617.
 [http://dx.doi.org/10.3390/molecules15053602] [PMID: 20657502]

[45]
Umesalma, S.; Sudhandiran, G. Ellagic acid prevents rat colon carcinogenesis induced by 1, 2 dimethyl hydrazine through inhibition of AKT-phosphoinositide-3 kinase pathway. Eur. J. Pharmacol.,  2011, 660(2-3), 249-258.
 [http://dx.doi.org/10.1016/j.ejphar.2011.03.036] [PMID: 21463623]

[46]
Wandall, H.H.; Tarp, M.A. Therapeutic cancer vaccines: Clinical trials and applications. In: Carbohydrate-based vaccines and immunotherapies; Guo, Z.; Boons, G.J., Eds.; Wiley & Sons, Inc.: Hoboken, New Jersey, 2009; pp. 333-355.
 [http://dx.doi.org/10.1002/9780470473283.ch11]

[47]
Alyar, S.; Adem, Ş. Synthesis, characterization, antimicrobial activity and carbonic anhydrase enzyme inhibitor effects of salicilaldehyde-N-methyl p-toluenesulfonylhydrazone and its Palladium(II), Cobalt(II) complexes. Spectrochim. Acta A Mol. Biomol. Spectrosc.,  2014, 131, 294-302.
 [http://dx.doi.org/10.1016/j.saa.2014.04.121] [PMID: 24835932]

[48]
Alyar, S.; Sen, C.H.; Alyar, H.; Adem, S.; Kalkanci, A.; Ozdemir, U.O. Synthesis, characterization, antimicrobial activity, carbonic anhydrase enzyme inhibitor effects, and computational studies on new Schiff bases of Sulfa drugs and their Pd(II), Cu(II) complexes. J. Mol. Struct.,  2018, 1171, 214-222.
 [http://dx.doi.org/10.1016/j.molstruc.2018.06.004]

[49]
Arslan, T.; Buğrahan Ceylan, M.; Baş, H.; Biyiklioglu, Z.; Senturk, M. Design, synthesis, characterization of peripherally tetra-pyridine-triazole-substituted phthalocyanines and their inhibitory effects on cholinesterases (AChE/BChE) and carbonic anhydrases (hCA I, II and IX). Dalton Trans.,  2020, 49(1), 203-209.
 [http://dx.doi.org/10.1039/C9DT03897C] [PMID: 31808483]

[50]
Arslan, T.; Türkoğlu, E.A.; Şentürk, M.; Supuran, C.T. Synthesis and carbonic anhydrase inhibitory properties of novel chalcone substituted benzenesulfonamides. Bioorg. Med. Chem. Lett.,  2016, 26(24), 5867-5870.
 [http://dx.doi.org/10.1016/j.bmcl.2016.11.017] [PMID: 27884694]

[51]
Esirden, İ.; Ulus, R.; Aday, B.; Tanç, M.; Supuran, C.T.; Kaya, M. Synthesis of novel acridine bis-sulfonamides with effective inhibitory activity against the carbonic anhydrase isoforms I, II, IX and XII. Bioorg. Med. Chem.,  2015, 23(20), 6573-6580.
 [http://dx.doi.org/10.1016/j.bmc.2015.09.022] [PMID: 26422787]

[52]
Kursun Aktar, B.S.; Oruc-Emre, E.E.; Demirtas, I.; Sahin Yaglioglu, A.; Karakucuk Iyidogan, A.; Guler, C.; Adem, S. Synthesis and biological evaluation of novel chalcones bearing morpholine moiety as antiproliferative agents. Turk. J. Chem.,  2018, 42(2), 482-492.
 [http://dx.doi.org/10.3906/kim-1705-28]

[53]
Lolak, N.; Akocak, S.; Bua, S.; Sanku, R.K.K.; Supuran, C.T. Discovery of new ureido benzenesulfonamides incorporating 1,3,5-triazine moieties as carbonic anhydrase I, II, IX and XII inhibitors. Bioorg. Med. Chem.,  2019, 27(8), 1588-1594.
 [http://dx.doi.org/10.1016/j.bmc.2019.03.001] [PMID: 30846402]

[54]
Özil, M.; Balaydın, H.T.; Şentürk, M. Synthesis of 5-methyl-2,4-dihydro-3H-1,2,4-triazole-3-one’s aryl Schiff base derivatives and investigation of carbonic anhydrase and cholinesterase (AChE, BuChE) inhibitory properties. Bioorg. Chem.,  2019, 86, 705-713.
 [http://dx.doi.org/10.1016/j.bioorg.2019.02.045] [PMID: 30836234]

[55]
Ekhteiari Salmas, R.; Mestanoglu, M.; Durdagi, S.; Sentürk, M.; Kaya, A.A.; Kaya, E.C. Kinetic and in silico studies of hydroxy-based inhibitors of carbonic anhydrase isoforms I and II. J. Enzyme Inhib. Med. Chem.,  2016, 31(1), 31-37.
 [http://dx.doi.org/10.3109/14756366.2014.1003216] [PMID: 25676327]

[56]
Turkan, F.; Cetin, A.; Taslimi, P.; Karaman, M.; Gulçin, İ. Synthesis, biological evaluation and molecular docking of novel pyrazole derivatives as potent carbonic anhydrase and acetylcholinesterase inhibitors. Bioorg. Chem.,  2019, 86, 420-427.
 [http://dx.doi.org/10.1016/j.bioorg.2019.02.013] [PMID: 30769267]

[57]
Alper Türkoğlu, E.; Şentürk, M.; Supuran, C.T.; Ekinci, D. Carbonic anhydrase inhibitory properties of some uracil derivatives. J. Enzyme Inhib. Med. Chem.,  2017, 32(1), 74-77.
 [http://dx.doi.org/10.1080/14756366.2016.1235043] [PMID: 28097897]

[58]
Tutar, U.; Koçyiğit, U.M.; Gezegen, H. Evaluation of antimicrobial, antibiofilm and carbonic anhydrase inhibition profiles of 1,3-bis-chalcone derivatives. J. Biochem. Mol. Toxicol.,  2019, 33(4), e22281.
 [http://dx.doi.org/10.1002/jbt.22281] [PMID: 30597695]

[59]
Güller, P.; Atmaca, U.; Güller, U.; Çalışır, U.; Dursun, F. Antibacterial properties and carbonic anhydrase inhibition profiles of azido sulfonyl carbamate derivatives. Future Med. Chem.,  2021, 13(15), 1285-1299.
 [http://dx.doi.org/10.4155/fmc-2020-0387] [PMID: 34075799]

[60]
Ahlskog, J.K.J.; Dumelin, C.E.; Trüssel, S.; Mårlind, J.; Neri, D. In vivo targeting of tumor-associated carbonic anhydrases using acetazolamide derivatives. Bioorg. Med. Chem. Lett.,  2009, 19(16), 4851-4856.
 [http://dx.doi.org/10.1016/j.bmcl.2009.06.022] [PMID: 19615903]

[61]
Abo-Ashour, M.F.; Eldehna, W.M.; Nocentini, A.; Ibrahim, H.S.; Bua, S.; Abou-Seri, S.M.; Supuran, C.T. Novel hydrazido benzenesulfonamides-isatin conjugates: Synthesis, carbonic anhydrase inhibitory activity and molecular modeling studies. Eur. J. Med. Chem.,  2018, 157, 28-36.
 [http://dx.doi.org/10.1016/j.ejmech.2018.07.054] [PMID: 30071407]

[62]
Qurrat-ul-Ain; Ashiq, U.; Jamal, R.A.; Saleem, M.; Mahroof-Tahir, M. Alpha-glucosidase and carbonic anhydrase inhibition studies of Pd(II)-hydrazide complexes. Arab. J. Chem.,  2017, 10(4), 488-499.
 [http://dx.doi.org/10.1016/j.arabjc.2015.02.024]

[63]
Srimai, V.; Ramesh, M.; Parameshwar, K.S.; Parthasarathy, T. Computer-aided design of selective Cytochrome P450 inhibitors and docking studies of alkyl resorcinol derivatives. Med. Chem. Res.,  2013, 22(11), 5314-5323.
 [http://dx.doi.org/10.1007/s00044-013-0532-5]

[64]
Abraham, D.J. Burger’s Medicinal Chemistry and Drug Discovery; Wiley Interscience: New york, 2003. 
 [http://dx.doi.org/10.1002/0471266949]

[65]
Kumar, N.; Mishra, S.S.; Sharma, C.S.; Singh, H.P. In silico ADME, bioactivity and toxicity analiysis of some selected antimalarial agents. Int. J. Appl. Pharm. Biol. Res.,  2016, 1(5), 1-8.

[66]
Palm, K.; Stenberg, P.; Luthman, K.; Artursson, P.I. Polar molecular surface properties predict the intestinal absorption of drugs in humans. Pharm. Res.,  1997, 14(5), 568-571.
 [http://dx.doi.org/10.1023/A:1012188625088] [PMID: 9165525]

[67]
Kremers, P. In vitro tests for predicting drug-drug interactions: The need for validated procedures. Pharmacol. Toxicol.,  2002, 91(5), 209-217.
 [http://dx.doi.org/10.1034/j.1600-0773.2002.910501.x] [PMID: 12570028]

[68]
Selick, H.E.; Beresford, A.P.; Tarbit, M.H. The emerging importance of predictive ADME simulation in drug discovery. Drug Discov. Today,  2002, 7(2), 109-116.
 [http://dx.doi.org/10.1016/S1359-6446(01)02100-6] [PMID: 11790621]

[69]
Pries, A.R.; Badimon, L.; Bugiardini, R.; Camici, P.G.; Dorobantu, M.; Duncker, D.J.; Escaned, J.; Koller, A.; Piek, J.J.; de Wit, C. Coronary vascular regulation, remodelling, and collateralization: Mechanisms and clinical implications on behalf of the working group on coronary pathophysiology and microcirculation. Eur. Heart J.,  2015, 36(45), 3134-3146.
 [http://dx.doi.org/10.1093/eurheartj/ehv100] [PMID: 26112888]

[70]
Camadan, Y.; Çiçek, B.; Adem, Ş.; Çalişir, Ü.; Akkemik, E. Investigation of in vitro and in silico effects of some novel carbazole Schiff bases on human carbonic anhydrase isoforms I and II. J. Biomol. Struct. Dyn.,  2021, 1-10.
 [http://dx.doi.org/10.1080/07391102.2021.1892527] [PMID: 33645441]

[71]
Sağlık, B.N.; Çevik, U.A.; Osmaniye, D.; Levent, S.; Çavuşoğlu, B.K.; Demir, Y.; Ilgın, S.; Özkay, Y.; Koparal, A.S.; Beydemir, Ş.; Kaplancıklı, Z.A. Synthesis, molecular docking analysis and carbonic anhydrase I-II inhibitory evaluation of new sulfonamide derivatives. Bioorg. Chem.,  2019, 91, 103153.
 [http://dx.doi.org/10.1016/j.bioorg.2019.103153] [PMID: 31382057]

[72]
Lipinski, C.A.; Lombardo, F.; Dominy, B.W.; Feeney, P.J. Experimental and computational approaches to estimate solubility and permeability in drug discovery and development settings. Adv. Drug Deliv. Rev.,  2001, 46(1-3), 3-26.
 [http://dx.doi.org/10.1016/S0169-409X(00)00129-0] [PMID: 11259830]

[73]
Ursu, O.; Rayan, A.; Goldblum, A.; Oprea, T. Understanding drug-likeness. WIREs Comput. Mol. Sci.,  2011, 1, 760-781.
 [http://dx.doi.org/10.1002/wcms.52]

Rights & Permissions Print Cite

Article Metrics

1

Journal Information

For Authors

For Editors

For Reviewers

Explore Articles

Open Access

Open Access Articles

For Visitors

DOI https://dx.doi.org/10.2174/1573409918666220818114505	Print ISSN 1573-4099
Publisher Name Bentham Science Publisher	Online ISSN 1875-6697

Current Computer-Aided Drug Design

In vitro Inhibition Profiles and Molecular Docking Analysis of Benzohydrazide Derivatives on Red Blood Cell Carbonic Anhydrases Isozymes

Abstract Play Pause

Graphical Abstract

Related Journals

Related Books

Abstract