Brand-new compound is hopeful to become fungi invincible opponent

Brand-new compound is hopeful to become fungi invincible opponent

Staff reporter Pan Xi

Organ transplant and diagnosis and general development and antibacterial medicine and the intersection of chemotherapy and wide application of medicine that treat of getting involved etc. until the intersection of immunity and defective patient increase, the incidence of the systemic fungal infection is rising year by year. But meanwhile, have and resist the using clinically limitedly in a large amount of the fungi medicine, it is serious to make the fungi produce the situation which is able to bear nature day by day.

Not long ago, supported by national natural science fund, PLA man second dean of army medical university medicine YuanYing Jiang lead scientific research personnel research and develop 2 - amino 4 the intersection of hydrogen and naphthalene type compound independently, expected to improve this state in the future, the research results are published on " China's pharmacology journal ".

"2- amino four the intersection of hydrogen and naphthalene compound have and not existing to resist fungi medicine totally different chemical constitution, though is the same as nitrogen thiazole medicine, make up composition Ergota steroid alcohol to produce, resist the function of fungi high-efficiently through inhibiting the important structure of the fungi cell membrane, but it is completely different from nitrogen thiazole medicine that its target of function is clicked. " A few days ago, participating in the second associate professor of army medical university College of Pharmacy soldier Cao Yong of PLA in research work interviews by " scientific Times ".

Able to bear nature and toxicity

Stimulate the new medicine to study

The fungi are that a big class have cell wall and very nuclear structure, do not divide the root, stem, leaf, do not include the chlorophyll, exist in the nature by way of depending on for a living or saprophytic, can carry on very nuclear cell type microorganism of the sexual or cloning.

According to U.S.A.'s relevant materials, the attacking bead fungus infects dyeing as most common 4 kinds ofth blood influenza in U.S.A., and already the main causes of death take place by the damaged organism of serious disease immunity person as leukemia and bone-marrow transplantation in attacking mildew of song. Except that the quantity of the common pathogenic fungal infection is increasing constantly, the infection that some rare or rare fungi cause is reported occasionally, so, increasingly much clinic and research work are all paying close attention to the prevention and cure of the fungal infection.

At present, it is mainly many alkene and nitrogen thiazole to have most frequently used resisting the fungi medicine clinically. Nitrogen thiazole uses the extensive resisting the fungi medicine most clinically, mainly act on wool steroid alcohol in the biosynthesis route of steroid alcohol of Ergota methyl enzyme, but this kind of medicine can bind with ferroheme iron atom of mammalian cell and lead to the fact the serious kidney of liver is malicious. Bead fungus resist fungi to the intersection of Fluorine and the intersection of health and the intersection of thiazole,etc. and commonly used the intersection of nitrogen and thiazole medicine able to bear medicine to be most common even, a great difficult problem already prevented and cured as systemic fungal infection.

In addition, many alkene medicines are " gold standard " of treating the fungal infection of serious disease ,But its serious urgent chronic bad reaction, for instance haemolysis, renal function are depleted, have limited its clinic use.

Cao YongBing introduces, in recent years, the morbidity of the systemic fungal infection obviously increases, cause the common bacterium of the systemic fungal infection to be able to bear the bacterial strain of medicine to expand constantly. The whole body fungal infection relates to reducing in immunological function of the organism, the patient because the immunological function is severed, even resist the fungi treatment for the strong experience, its prognosis is still very bad, the case fatality rate is up to more than 70%.

"But for many years, the research focus against fungi new medicine has mainly concentrated on preparation improving and modifying the structure of to the nitrogen thiazole to the many alkene, been failing to overcome the toxic question of the above-mentioned medicine fundamentally all the time. So, the new medicine studying brand-new structure and brand-new function target and clicking resists the outlet that the fungi medicine research and develop high-efficient, low-toxicitily. " Cao YongBing says.

Find the brand-new medicine target to click

"Some foreign large-scale drugmakers are studying new resisting the fungi medicine constantly too, medicine target order, have, act on to have, act on cell wall too cell membrane, but the price of these medicines is generally higher, and still produced medicine toxicity. " Cao YongBing says, the medicine function target that discovers this time is clicked, belong to the first time at home and abroad.

According to the introduction of Cao YongBing, some function targets of the original nitrogen thiazole medicine are fungi P450 enzyme in the body, P450 enzyme have detoxication, can poisonous substance metabolism a water soluble material lipid solubility usually, make the noxious substance discharge outside the body.

Cao explains in the army forever: "P450 enzyme exists in many kinds of organism, has this kind of enzyme in the human liver too. While the nitrogen thiazole medicine is killing the fungi, destroy P450 enzyme in the human liver too, thus produced medicine toxicity. "

"The original intention of research of ours, it is to hope to avoid target enzyme on function of original medicine, look for new the intersection of function and target order, with deepening that study, we find utilize 2 - amino four the intersection of hydrogen and naphthalene compound act on another kind of enzyme of fungi in the body, also can get up to the result, and does not produce liver toxicity. " Cao YongBing says.

Scientific research personnel utilize the gaseous phase chromatogram- The mass spectrum is united and used (GC/MS) Wait for technology, analyze 2 known at present - amino four hydrogen resist the intersection of fungi and the intersection of activity and most strong the intersection of compound and 2 - amino nonan - 6 - the intersection of methoxy and 4 the intersection of hydrogen and the intersection of naphthalene and the intersection of hydrochloric acid and salt ( 10b) in the naphthalene Biological influence of steroid alcohol of fungus Ergota of the dialogue bead.

The result shows, 2- amino nonane - 6 - methoxy four hydrogen naphthalene hydrochloric acid salt, through inhibiting the activity of alcohol C-14 reductase and relevant enzyme of C-5 desaturase of steroid doubly, make Ergota steroid alcohol biosynthesis reduce notably, thus destroy the integrality of the cell membrane and cause the death of fungi.

Say reduce MTS/PMS whether there aren't analytic approach Cao YongBing,though 2- 6 nonanes amino - can last cell activities mammalian dosage dependent at four hydrogen naphthalene hydrochloric acid salt methoxy, but the intersection of it and the intersection of dialogue and the intersection of bead and fungus most low to restrain fungus density lower than most low to inhibit the density from to mammalian cell far, this 2- amino nonane - 6 and methoxy four the intersection of hydrogen and the intersection of naphthalene and the intersection of hydrochloric acid and salt possible human body study, offer preliminary security in the future.

Need to update on later stage

Expert think 2 - amino 4 the intersection of hydrogen and naphthalene type compound have high-efficient, wide table, low-toxicity characteristic, and the function mechanism is unique, the liver kidney toxicity of preventing the nitrogen thiazole medicine from causing because of combining the ferroheme iron atom reacts. In addition, because its chemical constitution is different from existing resisting the fungi medicine, so, this kind compound will be overcome day by day effectively too the severe clinical fungi are able to bear the nature question.

But YongBing Cao think this but also one beginning only, still need going on to 2 - amino improvement of 4 the intersection of hydrogen and naphthalene type compound constantly future.

"Compared with existing medicine, the activity of this kind of compound is not strong enough at present, the ones that have not employed now have resisted the big medicine activity of fungi. In addition, it is a compound that this can only be called, can't be called medicines. Because the enzyme that compound act on his inhibitor store in and cross in different organism, also need to study. " Cao YongBing says.

Though there are a lot of subsequent research work, this research of the second College of Pharmacy of army medical university of PLA man establishes the foundation for developing and resisting the fungi medicine newly. Cao YongBing thinks, this benefits from in recent years the efforts that the fund supports is being strengthened constantly.

"In the past, the input to that a certain new medicine was researched and developed, it was only 100,000~20 ten thousand yuan. Can reach several million yuan even up to ten million yuan now. In addition, there are more projects that can apply, it was thousands of in one year originally, reach more than 10,000 now. There are more costs of scientific research in the research unit, this has improved scientific research personnel's enthusiasm to a great extent, also make the research and development process of new medicine much faster than the past. " Cao YongBing subsidizes personal feeling to the fund.

"We will go to try the new discovery constantly too in the future, will try to have new break-through in the medicine will be researched and developed. " Cao YongBing says.

Brand-new compound is hopeful to become fungi invincible opponent