Tüberküloz tedavisinde yeni ilaç adayları

Abstract

Tüberküloz, bütün dünyada önemli bir halk sağlığı sorunu olmaya devam etmekte olan, çok eski bulaşıcı ve ölümcül bir hastalıktır. Özellikle Afrika ve Asya ülkelerinde yaygın olarak görülen ve tüm dünyayı ilgilendiren bir sağlık sorunudur. Tüberkülozun giderek artan bir dünya sorunu olması; Mycobacterium tuberculosis zincirleri üzerindeki çoklu antibiyotik tedavisine karşı gelişen direncin artan şekilde devam etmesi ve HIV virüsüne bağlı olarak ortaya çıkan enfeksiyon nedeniyledir. Tüberküloz hastalığında tedavi en az altı ay süre ile çoklu ilaçlar ile gerçekleştirilmektedir. Tek ilaçla ve uygun olmayan süre yapılan tedavi ilaç direnci gelişimine yol açmaktadır. Tedavide kullanılan ilaçların uzun süre kullanılması ilaçların oluşturacağı yan etkiler açısından da risk oluşturmakta, ilaçların yan etkileri hastanın tedaviye uyumunu zorlaştırmakta ve bazen de hastanın tedaviyi bırakmasına neden olmaktadır. Bu nedenlerle hastalığın tedavisinde kullanılabilecek direnç gelişmemiş, etkili, tedavi süresini kısaltacak ve yan etkileri az olan yeni ilaçların bulunması şart olmuştur. 40 yıl gibi uzun bir aradan sonra ilk kez tedavide kullanılabilecek yeni bir ilaç etken maddesi “Bedaquiline” FDA tarafından Faz II aşamasındayken 2012 Aralık ayı sonunda onay almıştır. Bedaquiline çok ilaca dirençli tüberküloz tedavisinde kullanılacaktır. Bedaquiline’in ve yeni aday ilaçların yapıları incelendiğinde diarilkinolin, oksazolidinon, nitroimidazol, etilendiamin gibi ortak kimyasal yapılar dikkat çekmektedir. Bu ilaçların sahip olduğu ortak kimyasal yapılar yeni aday ilaçları tasarlarken yol gösterici olacaktır. Bu derlemede tüberküloz hastalığının tedavisinde kullanılmak üzere bedaquiline ve üzerinde preklinik ve daha ileri aşamalarda araştırma yapılan sutezolid, linezolid, PA-824, delamanid, rifapentin, gatifloksasin, moksifloksasin, BTZ-043, TBA-354, CPZEN-45, DC-159a, Q201, SQ-609, SQ-641 gibi yeni aday ilaçlardan bahsedilmiştir.

Keywords

• Tüberküloz, tedavi, aday ilaç

New drug candidates in tuberculosis treatment

Abstract

Tuberculosis is a very old infectious and mortal disease that continues to threaten the world. It is a growing health problem for all over the world although it has high prevalence mostly in poor African and Asian countries. This is because of the increasing pathology of tuberculosis with HIV and the resistance to antibiotic therapy. The treatment period is at least six months in tuberculosis. This causes the development of resistance to drugs and using multidrug therapy. The long duration of multidrug therapy creates a risk of side effects. The side effects of the drugs decrease the patient’s adherence to treatment and sometimes makes them quit the treatment. From these problems emerges the need for development of effective new drugs, with smaller duration of therapy, less side effects and without the problem of resistance. After a long period such as 40 years, a new drug molecule bedaquiline was approved in December 2012 by FDA while the drug was in phase II research. Bedaquiline will be used in multidrug resistant tuberculosis therapy. When the chemical structures of bedaquilline and other candidate drugs were examined, the structures such as diarylquinoline, oxazolidinone, nitroimidazole, ethylenediamine drew attention. These common structures will be directive in designing new molecules. In this review, bedaquiline and other candidate drug molecules such as sutezolide, linezolide, PA-824, delamanide, rifapentine, gatifloxacin, moxifloxacin, BTZ-043, TBA-354, CPZEN-45, DC-159a, Q201, SQ-609, SQ-641 were mentioned.

Keywords

• Tuberculosis, treatment, candidate drug

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