Abstract
Introduction: Mental disorders are very serious complicated disorders. Schizophrenia is one of the most baffling mental disorders. The new series 7-(2-(benzo[d]thiazol-2- ylamino)ethoxy)-4-methyl-2H-chromen-2- synthesized in search of newer compounds for Schizophrenia.
Methods: Synthesis is done by refluxing in dry pyridine with various substituted 2-amino benzothiazoles derivatives (3a-3k) and 7-(2-Chloroethoxy)-4-methyl-2H-chromen-2-one (2). The molecular docking approach was used to screen these generated derivatives. Chem Bio Draw Ultra 12 was used to draw the compounds, which were then exposed to all potential conformations of compounds interacting with receptors. The Glide 7.6, Schrodinger 2017 Maestro 11.3 was used to achieve molecular docking. The Dopamine receptor 6CM4 serotonin 5TUD PDBs were acquired from the database of Brookhaven Protein. Using the OPLS 2005 force field, the ligand-protein hydrogen-bond network was acquired, along with the overall energy reduced. A glide score was used to rate the docking poses.
Results: The produced compounds have been identified with the use of analytical and spectral data. All of the produced substances were tested and analyzed for serotonin 5HT2 antagonistic and dopamine D2 activity, which can be considered as a measure of typical antipsychotic properties.
Conclusion: Compounds 4b, 4c, 4e, 4g & 4i have demonstrated promising pharmacological action in preliminary studies. According to the preceding findings, compounds with electronwithdrawing substitutions, such as 4e & 4b, have a good atypical profile of antipsychotics.
Graphical Abstract
[1]
Glenon, R.A.; Westkaemper, R.B.; Bartyzel, P. Medicinal chemistry of serotonergic agents.Wiley- Liss; Peroutka, S.J., Ed.; New York, 1991, pp. 19-64.
[2]
Lourdes, S.; Eugenio, U.; Yagamare, F.; Marta, T.; Ro-Ragnar, T. Synthesis and structure-activity relationships of new aryl piperazines: Para substitution with electron-withdrawing groups decrease binding to 5-HT1A and D2A receptors. Eur. J. Med. Chem., 2002, 37(6), 503-510.
[http://dx.doi.org/10.1016/S0223-5234(02)01357-0] [PMID: 12204476]
[http://dx.doi.org/10.1016/S0223-5234(02)01357-0] [PMID: 12204476]
[4]
Gudelsky, G.A.; Nash, J.F.; Berry, S.A.; Meltzer, H.Y. Basic biology of clozapine: Electrophysiological and neuroendocrinological studies. Psychopharmacology, 1989, 99(S1)(Suppl.), S13-S17.
[http://dx.doi.org/10.1007/BF00442553] [PMID: 2682728]
[http://dx.doi.org/10.1007/BF00442553] [PMID: 2682728]
[5]
Hansen, J.B.; Fink-Jensen, A.; Christensen, B.V.; Grønvald, F.C.; Jeppesen, L.; Mogensen, J.P.; Nielsen, E.B.; Scheideler, M.A.; White, F.J.; Zhang, X-F. Mesolimbic selective antipsychotic arylcarbamates. Eur. J. Med. Chem., 1998, 33(11), 839-858.
[http://dx.doi.org/10.1016/S0223-5234(99)80009-9]
[http://dx.doi.org/10.1016/S0223-5234(99)80009-9]
[6]
Creese, I.; Burt, D.R.; Snyder, S.H. Dopamine receptor binding predicts clinical and pharmacological potencies of antischizophrenic drugs. Science, 1976, 192(4238), 481-483.
[http://dx.doi.org/10.1126/science.3854] [PMID: 3854]
[http://dx.doi.org/10.1126/science.3854] [PMID: 3854]
[7]
Hoyer, D.; Engel, G.; Kalkman, H.O. Molecular pharmacology of 5-HT1 and 5-HT2 recognition sites in rat and pig brain membranes: Radioligand binding studies with [3H]5-HT, [3H]8-OH-DPAT, (-)[125I]iodocyanopindolol, [3H]mesulergin e and [3H]ketanserin. Eur. J. Pharmacol., 1985, 118(1-2), 13-23.
[8]
Perouthka, S.J. Serotonin receptor subtypes: Basic and clinical aspects; Wiley-Liss: New York, USA, 1991, pp. 211-227.
[9]
Dumuis, A.; Gozlan, H.; Sebben, M.; Ansanay, H.; Rizzi, C.A.; Turconi, M.; Monferini, E.; Giraldo, E.; Schiantarelli, P.; Ladinsky, H.; Bockaert, J. Characterization of a novel 5-HT4 receptor antagonist of the azabicycloalkyl benzimidazolone class: DAU 6285. Naunyn Schmiedebergs Arch. Pharmacol., 1992, 345(3), 264-269.
[http://dx.doi.org/10.1007/BF00168685] [PMID: 1320204]
[http://dx.doi.org/10.1007/BF00168685] [PMID: 1320204]
[10]
Gawai, A.A.; Das, S.; Bhosale, S.H. Synthesis and pharmacological evalation of atypical antipsychotic activity of new coumarinoacetamides. Asian J. Res. Chem, 2010, 3(1), 166-171.
[11]
Gawai, A.A.; Bhosale, S.H. Synthesis and neuroleptic activity of new coumarinoacetamides. Ind J Heter Chem, 2006, 15, 267-270.
[12]
Bali, A.; Sen, U.; Peshin, T. Synthesis, docking and pharmacological evaluation of novel indole based potential atypical antipsychotics. Eur. J. Med. Chem., 2014, 74(3), 477-490.
[http://dx.doi.org/10.1016/j.ejmech.2013.09.020] [PMID: 24495776]
[http://dx.doi.org/10.1016/j.ejmech.2013.09.020] [PMID: 24495776]
[13]
Diouf, O.; Depreux, P.; Lesieur, D.; Poupaert, J.H.; Caignard, D.H. Synthesis and evaluation of new 2-piperazinylbenzothiaz oles with high 5-HT1A and 5-HT3 affinities. Eur. J. Med. Chem., 1995, 30(9), 715-719.
[http://dx.doi.org/10.1016/0223-5234(96)88289-4]
[http://dx.doi.org/10.1016/0223-5234(96)88289-4]
[14]
Kesten, S.R.; Heffner, T.G.; Johnson, S.J.; Pugsley, T.A.; Wright, J.L.; Wise, L.D. Design, synthesis, and evaluation of chromen-2-ones as potent and selective human dopamine D4 antagonists. J. Med. Chem., 1999, 42(18), 3718-3725.
[http://dx.doi.org/10.1021/jm990266k] [PMID: 10479303]
[http://dx.doi.org/10.1021/jm990266k] [PMID: 10479303]
[15]
Agnieszka, A.K.; Katarzyna, M.T.; Andrea, G.S.N.N. -(2-Hydroxyphenyl)-1-[3-(2-oxo-2,3-dihydro-1Hbenzimidazol-1-yl) propyl] piperidine-4-carboxamide (D2AAK4), a multi-target ligand of aminergic gpcrs, as a potential antipsychotic. Biomol, 2020, 10(349), 1-19.
[17]
Sreenivasa, G.M.; Jayachandran, E.S. Synthesis of bioactive molecule fluoro benzothiazole comprising potent heterocyclic moieties for anthelmintic activity. Arch Pharm Sci Res, 2009, 1(2), 150-157.
[18]
Jadhav, M.N.; Kokil, G.R.; Harak, S.S.; Wagh, S.B. Direct and indirect drug design approaches for the development of novel tricyclic antipsychotics: Potential 5-ht 2a antagonist. J. Chem., 2013, 2013, 1-8.
[http://dx.doi.org/10.1155/2013/930354]
[http://dx.doi.org/10.1155/2013/930354]
[19]
Campiani, G.; Butini, S.; Fattorusso, C. Pyrrolo[1,3] benzothiazepine-based serotonin and dopamine receptor antagonist. Molecular modeling, further structure-activity relationship studies, and identification of novel atypical antipsychotic agents. J. Med. Chem., 2004, 47(1), 143-157.
[20]
Palmer, M.J.; Deng, X.; Watts, S.; Krilov, G.; Gerasyuto, A.; Kokkonda, S.; El Mazouni, F.; White, J.; White, K.L.; Striepen, J.; Bath, J.; Schindler, K.A.; Yeo, T.; Shackleford, D.M.; Mok, S.; Deni, I.; Lawong, A.; Huang, A.; Chen, G.; Wang, W.; Jayaseelan, J.; Katneni, K.; Patil, R.; Saunders, J.; Shahi, S.P.; Chittimalla, R.; Angulo-Barturen, I.; Jiménez-Díaz, M.B.; Wittlin, S.; Tumwebaze, P.K.; Rosenthal, P.J.; Cooper, R.A.; Aguiar, A.C.C.; Guido, R.V.C.; Pereira, D.B.; Mittal, N.; Winzeler, E.A.; Tomchick, D.R.; Laleu, B.; Burrows, J.N.; Rathod, P.K.; Fidock, D.A.; Charman, S.A.; Phillips, M.A. Potent antimalarials with development potential identified by structure-guided computational optimization of a pyrrole-based dihydroorotate dehydrogenase inhibitor series. J. Med. Chem., 2021, 64(9), 6085-6136.
[http://dx.doi.org/10.1021/acs.jmedchem.1c00173] [PMID: 33876936]
[http://dx.doi.org/10.1021/acs.jmedchem.1c00173] [PMID: 33876936]
[21]
Madhavi Sastry, G.; Adzhigirey, M.; Day, T.; Annabhimoju, R.; Sherman, W. Protein and ligand preparation: Parameters, protocols, and influence on virtual screening enrichments. J. Comput. Aided Mol. Des., 2013, 27(3), 221-234.
[http://dx.doi.org/10.1007/s10822-013-9644-8] [PMID: 23579614]
[http://dx.doi.org/10.1007/s10822-013-9644-8] [PMID: 23579614]
[22]
Politzer, P.; Murray, J.S.; Clark, T. Halogen bonding and other σ-hole interactions: A perspective. Phys. Chem. Chem. Phys., 2013, 15(27), 11178-11189.
[http://dx.doi.org/10.1039/c3cp00054k] [PMID: 23450152]
[http://dx.doi.org/10.1039/c3cp00054k] [PMID: 23450152]
[23]
Abdulrahim, A.A.; Zain, A.M.; Mariam, A.M.; Elaf, A.K.; Fatima, A.E. Identification of novel plasmodium falciparum dihydroorotate dehydrogenase inhibitors for malaria using in silico studies; Scientific African, 2022, p. 24682276.
[http://dx.doi.org/10.1016/j.sciaf.2022.e01214]
[http://dx.doi.org/10.1016/j.sciaf.2022.e01214]
[24]
Ban, T.; Ohue, M.; Akiyama, Y. Multiple grid arrangement improves ligand docking with unknown binding sites: Application to the inverse docking problem. Comput. Biol. Chem., 2018, 73(73), 139-146.
[http://dx.doi.org/10.1016/j.compbiolchem.2018.02.008] [PMID: 29482137]
[http://dx.doi.org/10.1016/j.compbiolchem.2018.02.008] [PMID: 29482137]
[25]
Friesner, R.A.; Banks, J.L.; Murphy, R.B.; Halgren, T.A.; Klicic, J.J.; Mainz, D.T.; Repasky, M.P.; Knoll, E.H.; Shelley, M.; Perry, J.K.; Shaw, D.E.; Francis, P.; Shenkin, P.S. Glide: A new approach for rapid, accurate docking and scoring. 1. Method and assessment of docking accuracy. J. Med. Chem., 2004, 47(7), 1739-1749.
[http://dx.doi.org/10.1021/jm0306430] [PMID: 15027865]
[http://dx.doi.org/10.1021/jm0306430] [PMID: 15027865]
[26]
Davis, A.S.; Jenner, P.; Marsden, C.D. A comparison of motor behaviours in groups of rats distinguished by their climbing response to apomorphine. Br. J. Pharmacol., 1986, 87(1), 129-137.
[http://dx.doi.org/10.1111/j.1476-5381.1986.tb10164.x] [PMID: 3955297]
[http://dx.doi.org/10.1111/j.1476-5381.1986.tb10164.x] [PMID: 3955297]
[27]
Chung, W.; Park, J.B.; Kang, U.G.; Yong, S.K. Behavioural pharmacology of poly-galasaponins indicates potential antipsychotic efficacy. Pharmacol. Biochem. Behav., 2002, 71(1(2)), 191-195.
