Studies On The Activity Of Isoniazid Derivatives And Their Combinations With Other Anti-Tb Drugs On Mycobacterium Tuberculosis

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dc.contributor.authorParumasivam, Thaigarajan
dc.date.accessioned2018-10-19T01:54:42Z
dc.date.available2018-10-19T01:54:42Z
dc.date.issued2012-04
dc.description.abstractThe low permeability of the cell envelope against hydrophilic anti-tuberculosis (TB) drugs especially isoniazid (INH), is one of the crucial factors that contribute to the intrinsic resistance in Mycobacterium tuberculosis. Previous studies have floated the idea that the anti-mycobacterial activity of INH can be enhanced by augmenting the hydrophilic INH into a hydrophobic/lipophilic compound. Therefore, a series of 13 derivatives with different hydrophobicity were synthesized by adding different hydrophobic acyl chain to the parent compound, INH. The current study was aimed to investigate the anti-TB activity of these derivatives and their interactions with the first-line anti-TB drugs such as INH, streptomycin (STR), rifampicin (RIF) and ethambutol (EMB). The study was also aimed to elucidate the activity of potential hydrophobic INH derivative on the viability of M. tuberculosis H37Rv at the cellular level at different phases of the growth cycle. The cellular morphology of M. tuberculosis H37Rv ATCC 25618 during the growth cycle was best studied using solid medium as the growth stages were well defined compared to the liquid medium. The anti-TB activity of these derivatives was carried out by determining the minimum inhibitory concentration (MIC) against M. tuberculosis H37Rv using a tetrazolium microplate assay (TEMA). Among the derivatives tested, 1-isonicotinoyl-2-hexadecanoyl hydrazine (INH-C16), 1-isonicotinoyl-2-heptadecanoyl hydrazine (INH-C17) and 1-isonicotinoyl-2-octadecanoyl hydrazine (INH-C18) were shown to have two-fold lower MIC value than INH. Their interactions with first-line anti-TB drugs were then performed using a fixed-ratio isobologram method. INH-C16 showed most promising interaction with STR and RIF. Based on these findings, INH-C16 was selected for further studies on the cells. The results obtained indicated that M. tuberculosis H37Rv was most susceptible to INH-C16 at the lag, log and death phase of the growth cycle.en_US
dc.identifier.urihttp://hdl.handle.net/123456789/6814
dc.language.isoenen_US
dc.publisherUniversiti Sains Malaysiaen_US
dc.subjectThe low permeability of the cell envelopeen_US
dc.subjectagainst hydrophilic anti-tuberculosis drugsen_US
dc.titleStudies On The Activity Of Isoniazid Derivatives And Their Combinations With Other Anti-Tb Drugs On Mycobacterium Tuberculosisen_US
dc.typeThesisen_US
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