Tuberculosis chemotherapy: current drug delivery approaches

Tuberculosis is a leading killer of young adults worldwide and the global scourge of multi-drug resistant tuberculosis is reaching epidemic proportions. It is endemic in most developing countries and resurgent in developed and developing countries with high rates of human immunodeficiency virus infection. This article reviews the current situation in terms of drug delivery approaches for tuberculosis chemotherapy. A number of novel implant-, microparticulate-, and various other carrier-based drug delivery systems incorporating the principal anti-tuberculosis agents have been fabricated that either target the site of tuberculosis infection or reduce the dosing frequency with the aim of improving patient outcomes. These developments in drug delivery represent attractive options with significant merit, however, there is a requisite to manufacture an oral system, which directly addresses issues of unacceptable rifampicin bioavailability in fixed-dose combinations. This is fostered by the need to deliver medications to patients more efficiently and with fewer side effects, especially in developing countries. The fabrication of a polymeric once-daily oral multiparticulate fixed-dose combination of the principal anti-tuberculosis drugs, which attains segregated delivery of rifampicin and isoniazid for improved rifampicin bioavailability, could be a step in the right direction in addressing issues of treatment failure due to patient non-compliance

Synthesis of novel 1,3-diaryl-2-thioxanthine nucleoside analogs as adenosinergic agents

921-928A novel series of 1,3<span style="font-size:12.0pt;line-height:115%; font-family:" times="" new="" roman";mso-fareast-font-family:"times="" roman";="" color:#181818;mso-ansi-language:en-in;mso-fareast-language:en-in;mso-bidi-language:="" hi"="" lang="EN-IN">-diaryl-2-thioxanthine nucleosides , 1,3-diaryl-2-thio-9-(2'-tetrahydrofuranyl)/(2'-tetrahydropyranyl)xanthines 14-19, 1,3-diaryl-2-thio-9-(methoxymethyl)/(2' -chloroethoxymethyl)/(2'-chloroethyl) 6-13 and 1 -phenyl-2-methylthio-9-methoxymethyl-4-oxopurine <span style="font-size:12.0pt;line-height:115%;font-family: " times="" new="" roman";mso-fareast-font-family:"times="" roman";color:#181818;="" mso-ansi-language:en-in;mso-fareast-language:en-in;mso-bidi-language:hi"="" lang="EN-IN">have been synthesized. Condensation of 1,3-diaryl-2-thioxanthines 5a-c with dihydrofuran and dihydropyran gives 14-16 and 17-19 respectively in good yields. The reaction of some 5a-d separately with methoxymethylenechloride, <span style="font-size:12.0pt;line-height:115%;font-family: " times="" new="" roman";mso-fareast-font-family:"times="" roman";color:#181818;="" mso-ansi-language:en-in;mso-fareast-language:en-in;mso-bidi-language:hi"="" lang="EN-IN">1,2-dichloroethane and chloroethoxymethylenechloride yields <span style="font-size:12.0pt;line-height:115%; font-family:" times="" new="" roman";mso-fareast-font-family:"times="" roman";="" color:#181818;mso-ansi-language:en-in;mso-fareast-language:en-in;mso-bidi-language:="" hi"="" lang="EN-IN">the <span style="font-size:12.0pt;line-height:115%; font-family:" times="" new="" roman";mso-fareast-font-family:"times="" roman";="" color:#454545;mso-ansi-language:en-in;mso-fareast-language:en-in;mso-bidi-language:="" hi"="" lang="EN-IN">co<span style="font-size:12.0pt;line-height:115%; font-family:" times="" new="" roman";mso-fareast-font-family:"times="" roman";="" color:#181818;mso-ansi-language:en-in;mso-fareast-language:en-in;mso-bidi-language:="" hi"="" lang="EN-IN">rre<span style="font-size:12.0pt;line-height:115%; font-family:" times="" new="" roman";mso-fareast-font-family:"times="" roman";="" color:#545454;mso-ansi-language:en-in;mso-fareast-language:en-in;mso-bidi-language:="" hi"="" lang="EN-IN">s<span style="font-size:12.0pt;line-height:115%; font-family:" times="" new="" roman";mso-fareast-font-family:"times="" roman";="" color:#303030;mso-ansi-language:en-in;mso-fareast-language:en-in;mso-bidi-language:="" hi"="" lang="EN-IN">pond<span style="font-size:12.0pt;line-height:115%; font-family:" times="" new="" roman";mso-fareast-font-family:"times="" roman";="" color:#454545;mso-ansi-language:en-in;mso-fareast-language:en-in;mso-bidi-language:="" hi"="" lang="EN-IN">i<span style="font-size:12.0pt;line-height:115%; font-family:" times="" new="" roman";mso-fareast-font-family:"times="" roman";="" color:#181818;mso-ansi-language:en-in;mso-fareast-language:en-in;mso-bidi-language:="" hi"="" lang="EN-IN">n<span style="font-size:12.0pt;line-height:115%; font-family:" times="" new="" roman";mso-fareast-font-family:"times="" roman";="" color:#454545;mso-ansi-language:en-in;mso-fareast-language:en-in;mso-bidi-language:="" hi"="" lang="EN-IN">g <span style="font-size:12.0pt;line-height:115%; font-family:" times="" new="" roman";mso-fareast-font-family:"times="" roman";="" color:#303030;mso-ansi-language:en-in;mso-fareast-language:en-in;mso-bidi-language:="" hi"="" lang="EN-IN">1,3-di<span style="font-size:12.0pt;line-height:115%; font-family:" times="" new="" roman";mso-fareast-font-family:"times="" roman";="" color:#545454;mso-ansi-language:en-in;mso-fareast-language:en-in;mso-bidi-language:="" hi"="" lang="EN-IN">a<span style="font-size:12.0pt;line-height:115%; font-family:" times="" new="" roman";mso-fareast-font-family:"times="" roman";="" color:#303030;mso-ansi-language:en-in;mso-fareast-language:en-in;mso-bidi-language:="" hi"="" lang="EN-IN">ryl-2<span style="font-size:12.0pt;line-height:115%; font-family:" times="" new="" roman";mso-fareast-font-family:"times="" roman";="" color:#545454;mso-ansi-language:en-in;mso-fareast-language:en-in;mso-bidi-language:="" hi"="" lang="EN-IN">-<span style="font-size:12.0pt;line-height:115%; font-family:" times="" new="" roman";mso-fareast-font-family:"times="" roman";="" color:#303030;mso-ansi-language:en-in;mso-fareast-language:en-in;mso-bidi-language:="" hi"="" lang="EN-IN">thioxanthine <span style="font-size:12.0pt;line-height: 115%;font-family:" times="" new="" roman";mso-fareast-font-family:"times="" roman";="" color:#181818;mso-ansi-language:en-in;mso-fareast-language:en-in;mso-bidi-language:="" hi"="" lang="EN-IN">nucle<span style="font-size:12.0pt;line-height:115%; font-family:" times="" new="" roman";mso-fareast-font-family:"times="" roman";="" color:#454545;mso-ansi-language:en-in;mso-fareast-language:en-in;mso-bidi-language:="" hi"="" lang="EN-IN">osides <span style="font-size:12.0pt;line-height:115%; font-family:" times="" new="" roman";mso-fareast-font-family:"times="" roman";="" color:#181818;mso-ansi-language:en-in;mso-fareast-language:en-in;mso-bidi-language:="" hi"="" lang="EN-IN">6-9 <span style="font-size:12.0pt;line-height:115%; font-family:" times="" new="" roman";mso-fareast-font-family:"times="" roman";="" color:#303030;mso-ansi-language:en-in;mso-fareast-language:en-in;mso-bidi-language:="" hi"="" lang="EN-IN">,10<span style="font-size:12.0pt;line-height:115%; font-family:" times="" new="" roman";mso-fareast-font-family:"times="" roman";="" color:#303030;mso-ansi-language:en-in;mso-fareast-language:en-in;mso-bidi-language:="" hi"="" lang="EN-IN"> and <span style="font-size:12.0pt;line-height:115%; font-family:" times="" new="" roman";mso-fareast-font-family:"times="" roman";="" color:#181818;mso-ansi-language:en-in;mso-fareast-language:en-in;mso-bidi-language:="" hi"="" lang="EN-IN">11<span style="font-size:12.0pt;line-height:115%; font-family:" times="" new="" roman";mso-fareast-font-family:"times="" roman";="" color:#181818;mso-ansi-language:en-in;mso-fareast-language:en-in;mso-bidi-language:="" hi"="" lang="EN-IN"> <span style="font-size:12.0pt;line-height:115%; font-family:" times="" new="" roman";mso-fareast-font-family:"times="" roman";="" color:#454545;mso-ansi-language:en-in;mso-fareast-language:en-in;mso-bidi-language:="" hi"="" lang="EN-IN">a<span style="font-size:12.0pt;line-height:115%; font-family:" times="" new="" roman";mso-fareast-font-family:"times="" roman";="" color:#181818;mso-ansi-language:en-in;mso-fareast-language:en-in;mso-bidi-language:="" hi"="" lang="EN-IN">nd 12 <span style="font-size:12.0pt;line-height: 115%;font-family:" times="" new="" roman";mso-fareast-font-family:"times="" roman";="" color:#454545;mso-ansi-language:en-in;mso-fareast-language:en-in;mso-bidi-language:="" hi"="" lang="EN-IN">a<span style="font-size:12.0pt;line-height:115%; font-family:" times="" new="" roman";mso-fareast-font-family:"times="" roman";="" color:#181818;mso-ansi-language:en-in;mso-fareast-language:en-in;mso-bidi-language:="" hi"="" lang="EN-IN">nd 13 re<span style="font-size:12.0pt;line-height: 115%;font-family:" times="" new="" roman";mso-fareast-font-family:"times="" roman";="" color:#454545;mso-ansi-language:en-in;mso-fareast-language:en-in;mso-bidi-language:="" hi"="" lang="EN-IN">spec<span style="font-size:12.0pt;line-height:115%; font-family:" times="" new="" roman";mso-fareast-font-family:"times="" roman";="" color:#181818;mso-ansi-language:en-in;mso-fareast-language:en-in;mso-bidi-language:="" hi"="" lang="EN-IN">tively<span style="font-size:12.0pt;line-height:115%; font-family:" times="" new="" roman";mso-fareast-font-family:"times="" roman";="" color:#545454;mso-ansi-language:en-in;mso-fareast-language:en-in;mso-bidi-language:="" hi"="" lang="EN-IN">. <span style="font-size:12.0pt;line-height:115%; font-family:" times="" new="" roman";mso-fareast-font-family:"times="" roman";="" color:#181818;mso-ansi-language:en-in;mso-fareast-language:en-in;mso-bidi-language:="" hi"="" lang="EN-IN">The nucleo<span style="font-size:12.0pt;line-height:115%; font-family:" times="" new="" roman";mso-fareast-font-family:"times="" roman";="" color:#454545;mso-ansi-language:en-in;mso-fareast-language:en-in;mso-bidi-language:="" hi

Synthesis of purines and azapurines

1052-1065The synthesis of a series of C(8) unsubstituled <span style="font-size:17.0pt;mso-bidi-font-size: 9.0pt">(11a-h), C(8) substituted (<b style="mso-bidi-font-weight: normal">12a-e), <span style="font-size:16.5pt;mso-bidi-font-size: 8.5pt">8-mercapto (13a-e) <span style="font-size: 16.5pt;mso-bidi-font-size:8.5pt">1,3-diaryl-2- thioxanthines, as well as, 8-aza-1,3-diaryl-2-thioxanthines 1<span style="font-size:17.0pt;mso-bidi-font-size: 9.0pt">4a-g, through precursors, 5,6-diamino-1,3-diaryl-2-thiouracils <b style="mso-bidi-font-weight: normal">10 has been reported. Recently, the synthesis of a novel series of 6-amino-1,3-diaryl-2-thiouracils 8 under the influence of dry HCI gas has been reported. 14.15. These compounds are converted to the requisite 5,6-diamino-1,3-diaryl-2-thiouracils <b style="mso-bidi-font-weight: normal">10 via reduction of an intermediate 5-nitroso-6-amino-1,3-diaryl-2-thiouracils 9. Cyclocondensation of 5,6-diamino-2- thiouracils <span style="font-size: 17.0pt;mso-bidi-font-size:9.0pt;font-family:" times="" new="" roman";mso-fareast-font-family:="" "times="" roman";mso-ansi-language:en-us;mso-fareast-language:en-us;="" mso-bidi-language:ar-sa"="">10 <span style="font-size:16.5pt; mso-bidi-font-size:8.5pt;font-family:" times="" new="" roman";mso-fareast-font-family:="" "times="" roman";mso-ansi-language:en-us;mso-fareast-language:en-us;="" mso-bidi-language:ar-sa"="">with appropriate one carbon donors afford the desired purines 11<span style="font-size:17.0pt;mso-bidi-font-size:9.0pt; font-family:" times="" new="" roman";mso-fareast-font-family:"times="" roman";="" mso-ansi-language:en-us;mso-fareast-language:en-us;mso-bidi-language:ar-sa"="">-13.</span

<span style="font-size:20.5pt;mso-bidi-font-size:14.5pt; font-family:"Times New Roman";mso-fareast-font-family:"Times New Roman"; mso-ansi-language:EN-US;mso-fareast-language:EN-US;mso-bidi-language:AR-SA">Synthesis of novel 1,2-(un) substituted-3-amino-5-aryl-6-arylaminopyrazolo [3,4-<i style="mso-bidi-font-style:normal">d</i>]pyrimidin-4(5<i style="mso-bidi-font-style: normal">H</i>)-ones and their biological activities</span>

1075-1085A series of novel 1,2-(un)substituted -3-amino-5-aryl-6-arylaminopyrazolo[3,4-d<span style="font-size:16.5pt;mso-bidi-font-size:10.5pt;font-family:Arial;mso-bidi-font-style: italic">] pyrimidin-4(5H)-ones <b style="mso-bidi-font-weight: normal">5-7 has been synthesised through the cyclocondensation of the corresponding, hitherto unreported 3-aryl-2-arylamino-5-cyano-6- methyl sulfonylpyrimidin-4-ones 3 or 4 with hydrazine hydrate or substituted hydrazines. Compounds 6a and 7a exhibited analgesic activity superior to that of the standards, aspirin <span style="font-size:14.5pt; mso-bidi-font-size:8.5pt;font-family:Arial;mso-fareast-font-family:" times="" new="" roman";="" mso-ansi-language:en-us;mso-fareast-language:en-us;mso-bidi-language:ar-sa"="">& pentazocine. These compounds also exhibited significant antiinflammatory activity comparable to that of diclofenac sodium. The free radical scavenging activity, as well as, the ulcerogenic potential of some of the active compounds in the series was also determined.</span