Antitubercular activity

The antimicrobial activity of thiosemicarbazones against Mycobacterium tuberculosis in vitro was first reported by Domagk et al. [28] and later confirmed in vivo [29]. Screening revealed that only certain substituted be-nzaldehyde and heterocyclic thiosemicarbazones possess antitubercular activity [30-32]. The most widely used is p-acetamidobenzaldehyde thiosemicarbazone (trivial name = thiacetazone), 1. 

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The thiophene analog of chloramphenicol (255) has been synthesized,as also have been similar structures. The antibacterial activity of all was much lower than that of the natural antibiotic. The thioamide of 2-thenoic acid has been prepared in a study of potential antitubercular compounds. It did not surpass thioisonico-tinamide in antitubercular activity. The thiosemicarbazones of thio-phenealdehydes and ketones (cf. Section VII,D) show high activity against Mycobacterium tuberculosis, but are very toxic. The thiosemi-carbazone of 4-(2-thienyl)-3-buten-2-one has been reported to be capable of completely inhibiting the in vitro growth of M. tuberculosis even in relatively low concentrations. ... 

In order to investigate the antitubercular activity of thiophene analogs, thiosemicarbazones were synthesized 12). It was found that the addition of a small amount of acetic acid facilitated the reaction between thiosemicarbazide and the thiophene carbonyl compound and that the reaction was essentially completed in one half to one hour. The activities of these semicarbazones, however, were not recorded. 

Spirobenzothiazepines 302 were reported to have antifungal and antitubercular activity <2003CPB1137>. Oxazepines with antifungal properties are also known <2002BMCL1705, 2002BMCL27570>. 

Manvar AT, Pissurlenkar RR, Virsodia VR et al (2010) Synthesis, in vitro antitubercular activity and 3D-QSAR study of 1,4-dihydropyridines. Mol Divers 14 285-305... 

Antischistosomal activity, of 5-nitro-2-aminothiazoles, 72 Antispasmodic activity, 150, 439 Antitrichomonal activity, 138 of 5-nitro-2-aminothiazoles, 72 Antitubercular activity, 139, 140,441,442 Antitumor activity, 149, 152 Antitussive, 144, 148 Antiulcer properties, 148 Antiviral, 138, 139, 140, 144,438 Appetite depressant, 147 Aprotic solvent, see Solvent effect Aromatic aldehydes, with aminothiazoles, 40... 

A group of l,3,4-oxadiazolin-5-ones and l,3,4-oxadiazoline-5-thiones show antitubercular activity.18,43a 76,84 86,181, 132,157 160 They have been investigated with regard to their mode of action. 2-(4 -Pyridyl)-l,3,4-oxadiazolin-5-one (S 57) has shown itself active against Mycobacterium tuberculosis and Mycobacterium leprae.86-158 It possesses some advantages compared with isonicotinic acid hydrazide. Derivatives of S 57 also have some tuberculostatic activity.159, lfl1,162 Further tuberculostatic compounds are derived from p-aminosalicylic acid, for example WS 127 [2-(4 -amino-2 -hydroxyphenyl)-l,3,4-oxadiazoline-5-thione] and WS 174 [2-(4 -acetamido-2 -hydroxyphenyl)-l,3,4-oxadiazolin-5-one].85 2-Cyano-methyl-l,3,4-oxadiazolin-5-one shows a tuberculostatic activity comparable with that of Reazid. 18 Oxadiazolin-5-ones and oxa-... 

Although some guanylhydrazone-thiosemicarbazones showed high antitubercular activity, 176 did not. 6-Acyl- and 6-aroyl-5i7-1 -pyrin-dine-5,7(6//)-diones also react with hydrazine.112... 

The antitubercular activity of 2-carbamoylpyrazine and biological activity of pyrazines generally has been mentioned in Section 1.4. Certain pyrimidinyl derivatives of 2-carbamoylpyrazine have been shown to have lower toxicity and rather greater in vitro activity against Mycobacterium tuberculosis than 2-carbamoylpyrazine (1388), and the antitubercular activity of some extranuclear )V-substituted carbamoylpyrazines also showed a higher activity than 2-carbamoylpyrazine (1201). When tested on mice in vivo, 2-carbamoyl-5-methoxypyrazine and 2-hydrazino-carbonylpyrazine had less antitubercular activity than did 2-carbamoylpyrazine (1098) the antitubercular activities in a series of hydrazinocarbonyl-, carbamoyl-, and thiocarbamoylpyrazines have been examined and compared (1399). 

Answer E. For antitubercular activity, isoniazid (INH) must first be metabolically activated via a catalase present in mycobacteria. A decrease in expression of the cat G gene that encodes this enzyme is the mechanism of high-level resistance to INH. Low-level resistance occurs via mutations in the inh A gene that codes for an enzyme involved in synthesis of mycolic acids. Mutations in the gene that codes for DNA-dependent RNA polymerase is an important mechanism of resistance to rifampin and related antibiotics. 

Ans E For antitubercular activity, isoniazid (INH) must first be metabol-... 

A group of l,3,4-oxadiazolin-5-ones and l,3,4-oxadiazoline-5-thiones show antitubercular activity. ... 

Dihydro-6-alkoxy-3-aryl (or heteroaryl)-anthranils, e.g., 183, prepared by the action of hydroxylamine hydrochloride in pyridine on 3-alkoxy-6-acylcyclohex-2-en-l-ones, show antitubercular activity.260... 

As already indicated, many acylated quinoxalinethiones have been synthesized as potential pesticides/ Quinoxaline-2-thiones have been tested for antitubercular activity and 3-hydrazinoquinoxaline-2-thione has been incorporated into an antileprosy ointment/ Hydrazones of 3-hydrazinoquinoxaline-2-thione have antibacterial activity/... 

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