Alzheimer’s disease (AD) is the most common of the degenerative brain diseases and is described together with the impairment of cognitive function. Patients with AD lose the capability to code new memories, and life conditions are extremely difficult. The development of new drugs in this area continues at a great pace. A novel series of thiazole-piperazine hybrids, aimed against Alzheimer’s disease (AD), have been synthesized. The structure identification of synthesized compounds was elucidated by 1HNMR, 13C-NMR, and LCMSMS spectroscopic methods. The inhibitory potential of the synthesized compounds on cholinesterase enzymes was investigated. The compounds 3a, 3c and 3i showed significant inhibitory activity on the acetylcholinesterase (AChE) enzyme. On the other hand, none of the compounds showed significant inhibitory activity on the butyrylcholinesterase (BChE) enzyme. In addition to enzyme inhibition studies, enzyme kinetic studies were performed to observe the effects of the most active inhibitor compounds on the substrate–enzyme relationship. In addition to in vitro tests, docking studies also indicated that compound 3c potentially acts as a dual binding site AChE inhibitor.
INTRODUCTIONIn spite of a 5000 year history, tuberculosis (TB) remains the leading single-agent infectious disease killer in the world. Approximately one third of the world's population is infected with TB bacilli, and each year almost 8 million people develop active TB and 2 million die as a result of TB. The major challenges for tuberculosis control are the development of multidrug-resistant tuberculosis (MDRTB) strains and the increasing numbers of immunocompromised individuals with HIV infections who are highly susceptible to the disease. As a result, there is a pressing need for new antitubercular agents acting with greater potency and efficacy than the current existing drugs (1).To pursue this goal, our research efforts are directed to find new chemical classes of antimycobacterially active agents. The methods of investigation of structure-activity relationships (SARs) enabled us to find some new pharmacophores of the above-mentioned activity. Many studies were carried out on heterocyclic systems bearing a hydrazone structure as a pharmacophore (2-13). In this study, we planned to synthesize new molecules bearing hydr azone moieties for their potential antituberculosis activity. ChemistryThe synthetic route of the compounds is outlined in Scheme 1. For the synthesis of the title compounds, 5,6,7,8-tetrahydronaphthalene acetic acid hydrazide required as starting material was prepared by the reaction of 5,6,7,8-tetrahydronaphthalene acetic acid ethyl ester with hydrazine hydrate (14). The reaction of equimolar quantities of hydrazide with appropriate benzaldehydes in the presence of isopropyl alcohol resulted in the formation of the title compounds (A1-15) ( Table 1). Pharmacology Antituberculosis activity and CytotoxicityThe initial screen is conducted against Mycobacterium tuberculosis H37Rv (ATCC 27294) in BACTEC 12B medium using the Microplate Alamar Blue Assay (MABA) (15). One of the compounds showed significant antituberculosis activity as can be inferred from Table 2.The VERO cell cytotoxicity assay (16) is done in parallel with the TB Dose Response assay. Viabil-ABSTRACT: The heterocyclic hydrazone constitute an important class of biologically active drug molecules which have attractive attention of medicinal chemists due to their antituberculosis activities. For this purpose, new hydrazone derivatives were synthesized and evaluated for antituberculosis activity. The reaction of (5,6,7,8-tetrahydronaphthalen-1-yl) acetic acid hydrazide with various benzaldehydes gave 5,6,7,8-tetrahydronaphtalen acetic acid benzylidene hydrazide derivatives. The chemical structures of the compounds were elucidated by 1H-NMR, EI-MS spectral data and Elemental Analysis. The compounds were evaluated for antituberculosis activity against Mycobacterium tuberculosis H37Rv (ATCC 27294) using the BACTEC 460 radiometric system and BACTEC 12B medium. The preliminary results indicated that all of the tested compounds showed low activity against the test organism. The compound A10 showed high antituberculosis activity (IC50: 3.07...
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