Design, synthesis, and molecular docking study of benzothiazolotriazine derivatives for anticonvulsant potential

Abstract

A series of newer benzothiazolotriazine derivatives (4a-k) was designed, synthesized, and characterized as anticonvulsant agents against the two classically used MES and scPTZ animal models. The synthesized derivatives were tested in vivo in both the animal models, followed by a neurotoxicity study by the rotarod method. Compound 3,5]triazine was found most promising among the series in both the animal models, with no neurotoxicity. From this it may be confirmed that the presence of a methoxy (OCH 3 ) group at the lipophilic aryl ring was showing high anticonvulsant potency. In the molecular modeling study, compound 4e (docking score = −8.70) showed important hydrogen bond interaction with the amino acids LYS 329, SER 137, GLY 136 and π-π interactions with PHE 189 at the active site of GABA-AT. These derivatives can be further explored for the development of newer/novel anticonvulsant agents. K E Y W O R D S

Molecular docking of some benzothiazoles derivatives as anticonvulsant agents

“…Each ligand was determined to interact with the 1OHV active location, which was the highest mol dock, hydrogen bonding, and rerank scores used during docking. Table 1 demonstrates the general arrangement of the analogs [11][12][13][14].…”

Design, synthesis, and pharmacological evaluation of aryl oxadiazole linked 1,2,4-triazine derivatives as anticonvulsant agents

“…The animal test includes preliminary investigation (phase I screening) of MES and scPTZ and minimal motor inhibitory activity of the synthesized nal compounds as approved protocols provided by the Antiepileptic Drug Development (ADD) program by NINDS, USA. The dose of the test compounds was selected 30, 100 and 300mg/kg and were given to mice through intraperitoneal route and the response of the animals were recorded after an interval of 0.5 and 4 h [22][23][24]. The compounds found most potent in preliminary screening were further tested for phase II quantitative screening.…”

Solid‐Supported Materials‐Based Synthesis of 2‐Substituted Benzothiazoles: Recent Developments and Sanguine Future

“…Saeed Bahadorikhalili and Ali Reza Sardarian [239] used KF-Al 2 O 3 as a solid heterogeneous base catalyst and explored it in the synthesis of 2-substituted benzothiazole derivatives (19). The reaction of 2-aminothiophenol (18) with carboxylic acid derivatives such as acid chloride (21) or anhydride (116,117) resulted in the desired product. The effect of the catalyst on the reaction outcome was investigated in different solvents ACN, THF, DMF, DMSO, toluene and Et 2 O, and also under solvent-free conditions at varying temperatures.…”

“…Owing to the huge pharmacological significance associated with benzothiazole motif, several review articles were written on their synthetic methodologies and therapeutic potential [90–181] . We searched across various Web Engines such as SciFinder, Google Scholar, ScienceDirect and Pubmed with the keywords solid‐supported/Heterogeneous synthesis of benzothiazoles.…”

“…There were numerous review articles published in the literature encompassing the synthetic methodologies and pharmacological potential of benzothiazole scaffolds. Keri et al., [90] Choudhary et al., [91] Ali and Siddiqui, [92] Hisamoddin et al., [93] Jena, [94] Srivastava et al., [95] Gagoria et al., [96] Kamal et al., [97] Gjorgjieva et al., [98] Singh and Singh, [99] Pathak et al., [100] Sharma et al., [101] Rouf and Tanyeli, [102] Sompalle and Roopan, [103] Raju et al., [104] Tariq et al., [105] Abrol et al., [106] Irfan et al., [107] Temiz et al., [108] Wu et al., [109] Bhutani et al., [110] Bhat et al., [111] Sharma et al., [112] Bainsal et al., [113] Gupta et al., [114] Elamin et al., [115] Rana et al., [116] Firdaus et al., [117] Ammazzalorso et al., [118] Mohammad et al., [119] Satyadev et al., [120] Sumit et al., [121] Rouf et al., [102] Agarwal et al., [122] Kumar et al., [123] Asiri et al., [124] Amir et al., [125] Malik et al., [126] Agarwal et al., [127] and Azam et al [128] . published review articles on the developments of benzothiazole‐based scaffolds of pharmacological importance.…”