Synthesis and antimycobacterial activity of [5-(pyridin-2-yl)-1,3,4-thiadiazol-2-ylthio]acetic acid arylidene-hydrazide derivatives

doi:10.1016/S0014-827X(01)01097-7

Il Farmaco

Volume 56, Issue 8, 1 August 2001, Pages 587-592

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Abstract

[5-(Pyridin-2-yl)-1,3,4-thiadiazol-2-ylthio]acetic acid arylidene-hydrazide derivatives were synthesized and tested for their in vitro antimycobacterial activity. Some compounds showed a feable activity against a strain of Mycobacterium tuberculosis and a strain of Mycobacterium avium.

Introduction

The increase of tuberculosis due to emergence of multidrug-resistant strains (MDR) of Mycobacterium tuberculosis, together with the increased incidence of severe disseminated infections produced by mycobacteria other than tuberculosis (MOTT) in immunocompromised patients, have promted the search for new antimycobacterial drugs.

Continuing our search for new antimycobacterial agents, we synthesized a series of [5-(pyridin-2-yl)-1,3,4-thiadiazol-2-ylthio]acetic acid arylidene-hydrazide derivatives (4–37) (Table 1).

The synthesized compounds are characterized by the presence of the sequence (A) which partially resembles to pyridine-2-carboxamidrazone moiety, whose importance with respect to the antimycobacterial activity of a number of derivatives has been previously described [1], [2], [3], [4], [5], [6].

Moreover, the thioacetyl hydrazone moiety, linked to the 2 position of the 1,3,4-thiadiazole derivatives (4–37), was present in other compounds characterized by antibacterial and antifungal activity [7], [8] and hydrazido-hydrazone derivatives have been described for antimycobacterial properties [9].

The new synthesized compounds have been tested for their in vitro antimycobacterial activity towards a strain of Mycobacterium tuberculosis H₃₇Rv and a strain of Mycobacterium avium.

The activity of these compounds against a strain of Staphylococcus aureus, a strain of Escherichia coli and two strains of Candida albicans has been also evaluated.

Section snippets

Chemistry

The synthesis of [5-(pyridin-2-yl)-1,3,4-thiadiazol-2-ylthio]acetic acid arylidene-hydrazide derivatives (4–37) (Table 1) was carried out (Scheme 1) by treating pyridine-2-carboxamidrazone with carbon disulfide to obtain 5-(pyridin-2-yl)-3H-1,3,4-thiadiazole-2-thione 1 [10]. Compound 1 was reacted with ethyl bromoacetate to afford the [5-(pyridin-2-yl)-1,3,4-thiadiazol-2-ylthio]acetic acid ethylester (2), from which the [5-(pyridin-2-yl)-1,3,4-thiadiazol-2-ylthio]acetic acid hydrazide (3) was

Chemistry

Melting points were determined with a Büchi 510 capillary apparatus, and are uncorrected. Infrared spectra in nujol mulls were recorded on a Jasko FT 200 spectrophotometer. Proton nuclear magnetic resonance (¹H NMR) spectra were determined on a Varian Gemini 200 spectrometer; chemical shifts are reported as δ (ppm) relative to tetramethylsilane as internal standard, dimethylsulfoxide as solvent. Reaction courses and product mixtures were routinely monitored by thin-layer chromatography (TLC) on

Results and discussion

A series of [5-(pyridin-2-yl)-1,3,4-thiadiazol-2-ylthio]acetic acid arylidene-hydrazides (4–37) (Table 1) have been synthesized with the aim to evaluating their antimycobacterial activity (Table 3, Table 4) towards a strain of Mycobacterium tuberculosis (H₃₇Rv) sensitive to isoniazid and rifampicin and a strain of Mycobacterium avium resistant to ciprofloxacin and rifampicin. Only compounds 7, 8, 10, 12 and 16 exhibited a moderate in vitro antimycobacterial activity (MIC=20 μg/ml) against the

Acknowledgements

The authors would like to thank Dott. M. Cebulec for the microanalyses. This research was carried out with the financial support of the Italian M.U.R.S.T. (60%).

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Synthesis and antimycobacterial activity of [5-(pyridin-2-yl)-1,3,4-thiadiazol-2-ylthio]acetic acid arylidene-hydrazide derivatives

Abstract

Introduction

Section snippets

Chemistry

Chemistry

Results and discussion

Acknowledgements

Farmaco

Farmaco

Eur. J. Med. Chem.

Eur. J. Med. Chem.

Eur. J. Med. Chem.

Eur. J. Med. Chem.

Synthesis and antibacterial activity of aminoguanidine and amidrazone derivatives

Eur. J. Med. Chem.

Preliminary evaluation of in-vitro antimycobacterial properties of N1-(aryliden)-2-pyridinecarboxyamidrazones

J. Chemother.

Synthesis and antimycobacterial activity of some 2-pyridinecarboxyamidrazone derivatives

Farmaco