Uninzi lwezigulane zethu sele zisazi ngemfuneko eyandayo yamachiza amatsha e-antifungal; unyango lwezifo zokungunda ezifana ne-aspergillosis zinemida ebalulekileyo. Ubuthi, ukusebenzisana kweziyobisi, ukunganyangeki, kunye nedosi yiyo yonke imiba enokwenza unyango lube nzima; ke ngoko, okukhona sinokhetho lonyango olungaphezulu, kokukhona sinokufumana olona khetho lonyango lwezigulane. 

Ukuphuhlisa iziyobisi ze-antifungal kunzima ngenxa yokufana kwezinto eziphilayo phakathi kwabantu kunye nefungi; sabelana ngeendlela ezininzi zebhayoloji njengefungi, ukudala imiba ekuphuhliseni i-antifungals ekhuselekileyo. Ukuphuhlisa amachiza amatsha e-antifungal, abaphandi kufuneka bajonge indlela abanokusebenzisa ngayo ezinye zeeyantlukwano esinazo.

Apha ngezantsi kukho ukucazululwa komntu oqhelekileyo a uphononongo olusanda kupapashwa ejonge kumachiza asixhenxe e-antifungal okwangoku akumanqanaba ahlukeneyo ophuhliso. Uninzi lwama-antifungals amatsha luye lwaba ziinguqulelo ezintsha zamachiza amadala, kodwa ezi zixoxiwe kolu hlaziyo zineendlela ezintsha zesenzo kunye neerejimeni ezahlukeneyo zedosi, ke, ukuba zivunyiwe, la machiza anokubonelela ngethemba kwikamva elingekude kangako. imiqathango yonyango.

Rezafungin

I-Rezafungin okwangoku ikwisigaba sesi-3 sophuhliso. Lilungu leklasi ye-echinocandin yeziyobisi, kuquka i-micafungin kunye ne-caspofungin; I-Echinocandins isebenza ngokuthintela inxalenye yodonga lweseli lomngundo oluyimfuneko kwi-homeostasis.

I-Rezafungin iye yaphuhliswa ukuze igcine inzuzo yokhuseleko lwabaphambili bayo be-echinocandin; ngelixa uphucula iimpawu zayo ze-pharmacokinetic kunye ne-pharmacodynamic ukwenza unyango olukhethekileyo, olusebenza ixesha elide, oluzinzile oluvumela ukuba i-intravenous ngeveki kunokulawulwa kwemihla ngemihla, okunokwandisa ukhetho lonyango kwimeko yokuchasana kwe-echinocandin.

Fosmanogepix

I-Fosmanogepix yaziwa njengechiza lokuqala kwiklasi (ngokokuqala luhlobo lwe-antifungal) elithintela ukuveliswa kwekhompawundi ebalulekileyo ebalulekileyo ekwakhiweni kodonga lweseli kunye nokuzilawula. Ukuthintela ukuveliswa kwale khompawundi kwenza buthathaka udonga lweseli kangangokuba iseli ingakwazi ukosulela ezinye iiseli okanye ukuphepha amajoni omzimba. Okwangoku ikwiSigaba se-2 solingo lwezonyango kwaye ibonisa iziphumo ezithembisayo kunyango lomlomo kunye ne-intravenous ye-invasive fungal infections, ebonisa ukuphumelela kwi-multi-drug resistant kunye nezinye izifo ezinzima ukunyanga.

Olorifim

I-Olorifim iwela phantsi kodidi olutsha ngokupheleleyo lwamachiza e-antifungal ebizwa ngokuba yi-orotomides. I-orotomides inendlela eyahlukileyo yokusebenza, ngokukhetha ijolise kwi-enzyme ephambili kwi-pyrimidine biosynthesis. I-Pyrimidine iyimolekyuli ebalulekileyo kwi-DNA, i-RNA, udonga lweseli kunye ne-phospholipid synthesis, ukulawulwa kweeseli, kunye nokuveliswa kweprotheni, ngoko xa i-Olorofim ijolise kule enzyme, ichaphazela kakhulu i-fungi. Ngelishwa, i-Olorifim ayingobubanzi obubanzi, kwaye ibulala kuphela umngundo embalwa – ngokufanelekileyo, i-Aspergillus, kunye nokungunda okubangela ivalley fever (echaphazela ingqondo), iCoccidioides. Ukusukela oko yafunyaniswa, iye yaqhubela phambili kwizifundo zangaphambi kweklinikhi kunye nesigaba soku-1 solingo lwabantu kwaye sithetha nje sisigaba esiqhubekayo sesi-2 solingo lwezonyango oluvavanya ukusetyenziswa kwalo ngomlomo nangemithambo.

Ibrexafuningerp

Ibrexafungerp ngowokuqala kwiklasi entsha ye-antifungals ebizwa ngokuba yi-Triterpenoids. I-Ibrexafungerp ijolise kwilungu elifanayo elibalulekileyo lodonga lweseli yefungal eyenziwa yi-echinocandins, kodwa inesakhiwo esahluke ngokupheleleyo, esenza ukuba izinzile kwaye intsingiselo inokunikwa ngomlomo; Ukwahlula i-Ibrexafungerp kwii-echinocandins ezintathu ezikhoyo ngoku (i-caspofungin, i-micafungin, i-andulafungin), enokuthi inikwe kuphela nge-intravenously ukunciphisa ukusetyenziswa kwabo kwizigulane ezibhedlele kunye nezo zinokufikelela kwi-venous yokuhlala.

Kukho izilingo ezimbini eziqhubekayo zesigaba sesi-3 se-ibrexafungerp. Olona phando lubanzi kakhulu lokubhalisa ukuza kuthi ga ngoku luphononongo lwe-FURI, oluvavanya ukusebenza kunye nokhuseleko lwe-Ibrexafungerp phakathi kwezigulane ezinosulelo olunzima lomngundo kwaye ezingaphenduliyo okanye ezinganyamezeliyo i-antifungal agents eziqhelekileyo. Ukuqulunqwa komlomo kusanda kuvunywa yi-USA's Food and Drug Administration (FDA) kunyango lwe-vulvovaginal candidiasis (VVC).

Oteseconazole

I-Oteseconazole iyona yokuqala yee-agent ezininzi ze-tetrazole ezenzelwe ngenjongo yokukhethwa okukhulu, imiphumo embalwa yecala, kunye nokuphucula ukusebenza kakuhle xa kuthelekiswa ne-azoles ekhoyo ngoku. I-Oteseconazole yenzelwe ukubopha ngokuqinileyo kwi-enzyme ebizwa ngokuba yi-cytochrome P450. Xa besixoxa ngefungi yangaphambili kunye nabantu abafanayo, icytochrome P450 yenye yezo zifaniso. Iiseli zomntu ziqulethe iintlobo ezahlukeneyo ze-cytochrome P450, ezijongene nemisebenzi emininzi ebalulekileyo ye-metabolic. Ngoko ke, ukuba i-azole i-antifungal agents inqanda i-cytochrome yabantu i-P450, umphumo unokuba yimiphumo emibi. Kodwa, ngokungafaniyo nezinye i-azole antifungals, i-Oteseconazole inqanda kuphela i-cytochrome ye-fungal p450- kungekhona umntu ngenxa yobudlelwane bayo kwi-enzyme ekujoliswe kuyo (i-cytochrome P450) inkulu. Oku kufuneka kuthetha ukudibana okumbalwa kweziyobisi kunye netyhefu engaphantsi ngokuthe ngqo.

I-Oteseconazole ikwisigaba sesi-3 sophuhliso kwaye okwangoku iphantsi koqwalaselo lwe-FDA ukuze yamkelwe ukunyanga i-vulvovaginal candidiasis ephindaphindiweyo.

I-Encochleated Amphotericin B

Uninzi lwezigulane zethu ziya kuba sele bezinolwazi nge-Amphotericin B, ekhoyo ukusukela ngoo-1950. I-Amphotericin B iwela phantsi kodidi lwamachiza abizwa ngokuba yi-Polyenes- olona didi ludala lwamachiza e-antifungal akhoyo. Babulala umngundo ngokubophelela kwi-ergosterol esebenza ukugcina ingqibelelo yenwebu yeseli. Ichiza lisebenza ngokukhupha i-ergosterol, ibangela imingxunya kwi-membrane yeseli, iyenza ivuze ngokwaneleyo ukuba ingaphumeleli. Kodwa, ii-polyenes zikwanxibelelana ne-cholesterol kwiinwebu zeeseli zomntu, okuthetha ukuba zinetyhefu enkulu. I-Encochleated Amphotericin B iye yaphuhliswa ukuze igweme ezi tyhefu zibalulekileyo - i-novel lipid nanocrystal design ivumela ukuhanjiswa kweziyobisi ngokuthe ngqo kwizicubu ezosulelekileyo, ukukhusela umzimba ekuvezweni okungeyomfuneko - kwaye inokunikezelwa ngomlomo, inokunciphisa ukuhlala esibhedlele.

I-Encochleated Amphotericin B okwangoku ikwizigaba 1 & 2 zophuhliso, ngoko ke ikude kancinane. Nangona kunjalo, ithembisa ukubanakho kwechiza elithathwa ngomlomo ngokuncinci, ukuba kukho, ubuthi obuqhelekileyo be-amphotericin B.         

ATI-2307

I-ATI-2307 ikumanqanaba okuqala ophuhliso kwaye lichiza elitsha le-antifungal elinendlela eyodwa yokusebenza. I-ATI-2307 inqanda umsebenzi we-mitochondrial (i-mitochondria zakhiwo ngaphakathi kweeseli eziguqula ukutya zibe amandla), ukunciphisa ukuveliswa kwe-ATP (i-adenosine triphosphate), eyona molekyuli ephethe amandla, ekhokelela ekuthinteleni ukukhula.

Njengoko bekutshiwo ngaphambili, i-ATI-2307 isekwinqanaba lokuqala. Sekunjalo, abaphandi baye bagqiba izifundo ezintathu zeklinikhi zeSigaba soku-1 ezibonise ukuba zinyanyezelwe kakuhle ebantwini kumanqanaba edosi yonyango elindelekileyo. Ngaloo ndlela, indima yeklinikhi ye-ATI-2307 ayicacanga; nangona kunjalo, umsebenzi wayo obanzi we-in vitro ngokuchasene nentaphane yezinto ezibalulekileyo zokungunda, kubandakanywa izilwanyana ezininzi ezixhathisa iziyobisi, zinokuguqulela indima ebalulekileyo kule khompawundi, ngakumbi kusulelo lomngundo ngenxa yezinto eziphilayo ezixhathisayo njenge-azole-resistant Aspergillus.