Anti-tubercular activity

Pyrolyses and thermal stabilities of 2-hydroxy-, 2-ethoxy-, and 2-isopropoxy-pyrazines have been studied. 2-Hydroxypyrazine was very stable, but the alkoxy-pyrazines underwent thermal elimination of olefin to yield 2-hydroxypyrazine (668a). Electrochemical reductions of l-methyl-2-oxo-5,6-diphenyl-l,2-dihydro-pyrazine and 54iydroxy(and 5-methoxy)-2,3-diphenylpyrazine are reported to involve the intermediate enamine, for example, 6-hydroxy-1-methyl-2,3-diphenyl-1,4-dihydropyrazine (54) (1096, cf. 1097). When tested on mice 2-carbamoyl-5-methoxypyrazine had less anti tubercular activity than did pyrazinamide (1098). 

Various parts of M. oleifera are identified for innumerable pharmacological properties viz. antimicrobial activity (12, 134). The juice from the leaves and stem bark of M. oleifera inhibit Staphylococcus aureus but not Escherichia coli (50). The fresh leaf juice inhibits the growth of pathogenic Pseudomonas aeruginosa and Staphylococcus aureus (21, 143). The bark extract possesses anti-fungal and anti-tubercular activity (50). Niaziridin rich fraction of M. oleifera pods enhances the bioactivity of commonly used antibiotics such as rifampicin, tetracycline and ampicillin against gram(+) and (-) bacteria (37). 

W. S. Johnson, Chelating Properties of Some NN -Disubstituted Thioureas having Anti-tubercular Activity, Thesis (University of Kentucky Press, Lexington, KT, 1966). 

A series of 1,4-dihydropyridines 149 bearing pyrazole derivatives was shown to have anti-tubercular activity against Mycobacterium tuberculosis H37Rv. ... 

Prior to 1940 copper oxide has been successfully used in the treatment of tuberculosis. However, in 1940, several additional Cu complexes were reported to have anti-tubercular activity and one of them, the Cu complex, sodium 3-(allylcuprothioureido)benzoate (allocupreide sodium, Cupralene, 19% Cu, 1) was suggested to be superior to gold (Au) therapy of tuberculosis [46—48]. 

B.P. Rao, S. Sarasija, and C. Narendra, Physicochemical characterization of Hydroxypropyl-P-cyclodextrin complexes of Rifampicin for improved anti-tubercular activity and stability, Indian Drugs., 43 (8), 679-682, 2006. 

Imtamovsky A, Polanc S, Vinsova J, Kocevar M, JampUek J, Reckova Z, Kaustova J (2007) A new modification of anti-tubercular active molecules. Biooig Med Chem 15 2551-2559... 

Other workers have demonstrated improved lung function (including arterial oxygen level increase [355]) and increased response to bronchodilators [356] after bromhexine. Some evidence of weak activity against tubercle bacillus has appeared [357] this could complicate culture control of anti-tubercular therapy. 

The cyclisation of ethylenediamine (ED) and propyleneglycol (PG) to 2-methy lpyrazine (MP) is a fundamental step for the catalytic synthesis of 2-amidopyrazine (AP), a well-known anti-tubercular drug. The formation of MP takes place in vapour-phase at ca. 650 K, atmospheric pressure and in excess of steam over a Zn-Cr-O(Pd) catalyst. The exploratory research and optimisation of the catalyst [1-6] led to a proper procedure for the activation of the latter and to the determinat ion of the optimal range of reaction conditions. The present work describes an extended study, aiming at throwing light on the intimate mechanism of the process. 

Hevener KE, Ball DM, Buolamwini JK, Lee RE (2008) Quantitative structure-activity relationship studies on nitrofuranyl anti-tubercular agents. Bioorg Med Chem 16 8042-8053... 

Isoniazid [eye soe NYE a zid], the hydrazide of isonicotinic acid, is a synthetic analog of pyridoxine. It is the most potent of the anti-tubercular drugs, but is never given as a single agent in the treatment of active tuberculosis. Its introduction revolutionized the treatment of tuberculosis. 

Our motivation for investigating thioamide derivatives, which potentially can form N-H... S interactions, arises from the presence of the -N(H)-C(=S)- residue, and derivatives thereof, in several dmgs [20], see Scheme 6.2 for chemical structures of these species. Thus, the antithyroid drugs 6-n-propyl-thiouracil (I) and l-methyl-3//-imidazole-2-thione (II, Methimazole , also marketed as Tapazole ) feature the -N(H)-C(=S)- functional group [21]. Hyperthyroidism may be treated with 3-methyl-2-thioxo-4-imidazoline-l-carboxylate (III, Carbimazole ) which is metabolised in vivo to the active form, known as Methimazole [22]. Anti-tubercular agents containing the thioamide residue and which inhibit mycolic acid synthesis include 2-ethyl-thioisonicotinamide (IV, Ethionamide ) and its -propyl derivative (Prothionamide ) [23-25]. 

---