Synthesis of some novel hydrazone derivatives and evaluation of their antituberculosis activity

Abstract

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...

Microwave assisted synthesis of some novel Flurbiprofen hydrazide hydrazones as anti-HCV NS5B and anticancer agents

“…Hydrazidehydrazones and their derivatives are versatile molecules with broad spectrum biological activities (7)(8)(9)(10). Previously, we had synthesized a panel of flurbiprofen hydrazide-hydrazone derivatives and observed that they inhibited hepatitis C virus (HCV) NS5B RNA-dependent RNA polymerase (RdRp) activity by 20-50% at 200 μM concentration (11).…”

Pharmacologically potentials of hydrazonone containing compounds: a promising scaffold

“…During the coumarin-4-acetic acid benzylidene hydrazides as anti-TB agents against Mtb H37Rv strain, (7-Hydroxy-2-oxo-2H-chromen-4-yl)-acetic acid (3-nitro-benzylidene) hydrazide [38] was found to be most potent (Manvar et al, 2008). Some 5, 6, 7, 8-tetrahydronaphthalen acetic acid benzylidene hydrazide derivatives showed anti-TB activity and compounds having -OH and -NO 2 in ortho and Meta position of aromatic ring having high anti-TB activity (Ozemir et al, 2010). Aryl acetic acid hydrazones showed moderate activity against Mtb H37 RV strain (Srivastava et al, 2010).…”

“…The anticonvulsant potential of some hydrazone derivatives [91], [92] having long duration of action and a rapid onset of action (Kaushik et al, 2010). Antidepressant activity of hydrazones [93] has been reported (de Oliveira et al, 2011). The in-vitro β-amyloid aggregation inhibitory activity showed by hydrazone derivatives [96] with an IC 50 of 23μM (Catto et al, 2010).…”

Biological Activities of Hydrazone Derivatives in the New Millennium

“…Treatment options for these infections are often limited, especially in debilitated and immunocompromised patients. AhmetOzdemir et al (2010) synthesized some novel hydrazone derivatives by the reaction of (5,6,7,8-tetrahydronaphalen-1-yl) acetic acid hydrazide with various benzaldehydes which gave 5,6,7,8-tetrahydronaphthalen acetic acid benzylidenehydrazide derivatives and evaluated their antituberculosis activity which showed that compounds having -OH and -NO2 in ortho and meta position of aromatic ring having high antituberculosis activity and low cytotoxicity 27 . SrivsatavaRitu et al (2010) synthesized twelve aryl acetic acid hydrazonesand tested first time for their activity against mycobacterium.…”