Computer-aided synthesis of dapsone-phytochemical conjugates against dapsone-resistant Mycobacterium leprae

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Dapsone resistance in Mycobacterium leprae.

The folP1 gene of Mycobacterium leprae, which encodes dihydropteroate synthase (DHPS), was studied for the presence of mutations associated with resistance to dapsone (DDS). When the folP1 of several DDS-resistant clinical isolates of M. leprae were sequenced, two missense mutations were identified. One mutation occurred at codon 53, substituting isoleucine for threonine in DHPS-1, and a second...

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Activity of derivatives and analogs of dapsone against Mycobacterium leprae.

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Dapsone (4,4'-diaminodiphenylsulfone), incorporated into the mouse chow in a concentration of 0.1 g/100 g of diet, was administered for 1 week to mice in which Mycobacterium leprae had multiplied to the level of 10(6) organisms/footpad. M. leprae were harvested from these and also from control mice, diluted serially, and inoculated into additional mice. The organisms recovered from untreated mi...

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Dihydropteroate synthase of Mycobacterium leprae and dapsone resistance.

Two Mycobacterium leprae genes, folP1 and folP2, encoding putative dihydropteroate synthases (DHPS), were studied for enzymatic activity and for the presence of mutations associated with dapsone resistance. Each gene was cloned and expressed in a folP knockout mutant of Escherichia coli (C600DeltafolP::Km(r)). Expression of M. leprae folP1 in C600DeltafolP::Km(r) conferred growth on a folate-de...

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Increase in prevalence of leprosy caused by dapsone-resistant Mycobacterium leprae.

The prevalence o f secondary resistance o f Mycobacterium leprae to dapsone (among leprom atous leprosy patients treated fo r a m inim um o f 5 years) has been estimated, from sur­ veys conducted before 1976 , to be 2 .5 /1 0 0 patients at risk in Malaysia, 3 /1 0 0 in Israel, 7 /1 0 0 in Costa Rica, and at least 1 0 /1 0 0 in Ethiopia. Apparent prim ary resistance to dapsone (among patients no...

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ژورنال

عنوان ژورنال: Scientific Reports

سال: 2020

ISSN: 2045-2322

DOI: 10.1038/s41598-020-63913-9