Iningi leziguli zethu seliyazi kakade ngesidingo esandayo semithi emisha ye-antifungal; Ukwelashwa kwezifo zesikhunta njenge-aspergillosis kunemikhawulo ebalulekile. Ubuthi, ukusebenzisana kwezidakamizwa, ukumelana, kanye nomthamo yizo zonke izindaba ezingenza ukwelashwa kube nzima; ngakho-ke, uma sinezinketho zokwelashwa ezengeziwe, maningi amathuba okuba sithole inketho yokwelapha ephelele yeziguli. 

Ukuthuthukisa izidakamizwa ze-antifungal kunzima ngenxa yokufana kwezinto eziphilayo phakathi kwabantu nesikhunta; sabelana ngezindlela eziningi zebhayoloji njengesikhunta, sidala izinkinga ekuthuthukiseni ama-antifungal aphephile. Ukuze bakhe imithi emisha ye-antifungal, abacwaningi kufanele babheke ukuthi bangasebenzisa kanjani omunye umehluko esinawo.

Ngezansi ukuhlukaniswa kwe-a isibuyekezo esisanda kushicilelwa ebheke izidakamizwa eziyisikhombisa ze-antifungal okwamanje ezisezigabeni ezihlukahlukene zokukhula. Iningi lama-antifungal amasha kube yizinguqulo ezintsha zemithi emidala, kodwa lezo okuxoxwe ngazo kulokhu kubuyekezwa zinezinqubo ezintsha zokwenza kanye nezinhlobo ezahlukene zemithamo, ngakho-ke, uma kuvunyiwe, le mithi inganikeza umsebe wethemba esikhathini esizayo esingekude kangako. imigomo yokwelashwa.

Rezafungin

I-Rezafungin okwamanje isesigabeni sesi-3 sokuthuthuka. Kuyilungu leqembu le-echinocandin lezidakamizwa, okuhlanganisa i-micafungin ne-caspofungin; Ama-Echinocandins asebenza ngokuvimbela ingxenye yodonga lwamaseli esikhunta ebalulekile ku-homeostasis.

I-Rezafungin yenzelwe ukugcina izinzuzo zokuphepha zabanduleli bayo be-echinocandin; ngenkathi ithuthukisa izakhiwo zayo ze-pharmacokinetic kanye ne-pharmacodynamic ukuze udale ukwelashwa okuyingqayizivele, okuthatha isikhathi eside, okuzinzile okuvumela ukufakwa kwe-intravenous masonto onke kunokulawulwa kwansuku zonke, okungase kwandiswe izinketho zokwelapha ekumisweni kokumelana kwe-echinocandin.

I-Fosmanogepix

I-Fosmanogepix yaziwa njengomuthi wesigaba sokuqala (owokuqala wohlobo lwawo lwe-antifungal) ovimba ukukhiqizwa kwenhlanganisela ebalulekile ebalulekile ekwakhiweni kodonga lwamaseli kanye nokuzilawula. Ukuvimbela ukukhiqizwa kwalesi sakhi kwenza buthaka udonga lwengqamuzana kangangokuthi ingqamuzana alisakwazi ukuthelela amanye amangqamuzana noma ukugwema amasosha omzimba. Njengamanje isesigabeni sesi-2 sokuhlolwa kwemitholampilo futhi ibonisa imiphumela ethembisayo ekwelapheni ngomlomo nangokufakwa emthanjeni kwezifo eziningi zesikhunta ezihlaselayo, okubonisa ukusebenza kahle kokumelana nezidakamizwa eziningi nezinye izifo okunzima ukukwelapha.

I-Olorifim

I-Olorifim iwela ngaphansi kwesigaba esisha ngokuphelele semithi elwa namagciwane ebizwa ngokuthi i-orotomide. Ama-orotomide anendlela ehlukile yokusebenza, ngokukhetha aqondise i-enzyme eyinhloko ku-pyrimidine biosynthesis. I-Pyrimidine iyi-molecule ebalulekile ku-DNA, i-RNA, udonga lwamaseli kanye ne-phospholipid synthesis, ukulawulwa kwamaseli, nokukhiqizwa kwamaprotheni, ngakho-ke lapho i-Olorofim ihlose le enzyme, ithinta kakhulu isikhunta. Ngeshwa, i-Olorifim ayiwona obanzi, futhi ibulala kuphela isikhunta esimbalwa - ngokufanelekile, i-Aspergillus, kanye nesikhunta esibanga i-valley fever (ehlasela ubuchopho), i-Coccidioides. Selokhu yatholakala, iye yathuthuka ngezifundo zangaphambi komtholampilo kanye nokuhlolwa kwabantu kwesigaba 1 futhi okwamanje iyisivivinyo somtholampilo esiqhubekayo sesigaba sesi-2 esihlola ukusetshenziswa kwayo ngomlomo nangemithambo yegazi.

Ibrexafuningerp

I-Ibrexafungerp ingeyokuqala yekilasi elisha lama-antifungal abizwa nge-Triterpenoids. I-Ibrexafungerp iqondise ingxenye ebalulekile yodonga lweseli lokukhunta eyenziwa yi-echinocandin, kodwa inesakhiwo esihluke ngokuphelele, iyenza iqine futhi isho ukuthi inganikezwa ngomlomo; ukwehlukanisa i-Ibrexafungerp kuma-echinocandin amathathu atholakalayo njengamanje (i-caspofungin, i-micafungin, i-andulafungin), enganikezwa kuphela ngomthambo okunciphisa ukusetshenziswa kwawo ezigulini ezilaliswe esibhedlela kanye nalezo ezinokungena kwe-venous engaphakathi.

Kunezilingo ezimbili eziqhubekayo zesigaba sesi-3 ze-ibrexafungerp. Ucwaningo olubanzi kakhulu lokubhalisa kuze kube manje ucwaningo lwe-FURI, oluhlola ukusebenza kahle nokuphepha kwe-Ibrexafungerp phakathi kweziguli ezinokutheleleka okukhulu kwesikhunta futhi ezingaphenduli noma ezingabekezeleli ama-ejenti ajwayelekile e-antifungal. Ukwakhiwa komlomo kusanda kugunyazwa yi-USA's Food and Drug Administration (FDA) yokwelapha i-vulvovaginal candidiasis (VVC).

I-Oteseconazole

I-Oteseconazole ingeyokuqala kwama-ejenti amaningana e-tetrazole aklanywe ngomgomo wokukhetha okukhulu, imiphumela engemihle embalwa, nokusebenza okuthuthukisiwe uma kuqhathaniswa nama-azole atholakalayo njengamanje. I-Oteseconazole yakhelwe ukubophezela ku-enzyme ebizwa ngokuthi i-cytochrome P450. Lapho sixoxa ngesikhunta sangaphambilini kanye nabantu abafana, i-cytochrome P450 ingenye yalezo zinto ezifanayo. Amaseli omuntu aqukethe izinhlobo ezahlukene ze-cytochrome P450, ezinesibopho semisebenzi eminingi ebalulekile ye-metabolic. Ngakho-ke, uma ama-azole antifungal agents evimbela i-cytochrome P450 yomuntu, umphumela ungaba ukusabela okubi. Kodwa, ngokungafani nezinye i-azole antifungals, i-Oteseconazole ivimbela kuphela i-fungal cytochrome p450- hhayi yomuntu ngenxa yokuhlobana kwayo kwe-enzyme ehlosiwe (cytochrome P450) inkulu. Lokhu kufanele kusho ukusebenzisana kwezidakamizwa okumbalwa kanye nobuthi obuqondile obuncane.

I-Oteseconazole isesigabeni sesi-3 sokuthuthukiswa futhi okwamanje ingaphansi kokucatshangelwa kwe-FDA ukuze igunyazwe ukwelapha i-vulvovaginal candidiasis ephindaphindayo.

I-Encochleated Amphotericin B

Iziguli zethu eziningi zizobe seziyazi kakade i-Amphotericin B, ebilokhu ikhona kusukela ngeminyaka yawo-1950. I-Amphotericin B iwela ngaphansi kwesigaba semithi ebizwa ngokuthi i-Polyenes- isigaba esidala kakhulu semithi elwa namagciwane etholakalayo. Babulala isikhunta ngokubopha i-ergosterol esebenza ukugcina ubuqotho bolwelwesi lwamaseli. Umuthi usebenza ngokukhumula i-ergosterol, ubangele izimbobo kulwelwesi lweseli, ulenze livuze ngokwanele ukuba lihluleke. Kodwa, ama-polyenes nawo asebenzisana ne-cholesterol kulwelwesi lwamaseli omuntu, okusho ukuthi anobuthi obubalulekile. I-Encochleated Amphotericin B yenzelwe ukugwema lobu buthi obubalulekile - umklamo wayo wenoveli we-lipid nanocrystal uvumela ukulethwa kwezidakamizwa ngqo ezicutshini ezithelelekile, ukuvikela umzimba ekuchayekeni okungadingekile - futhi inganikezwa ngomlomo, okungenzeka kunciphise ukuhlala esibhedlela.

I-Encochleated Amphotericin B okwamanje isesigabeni 1 & 2 sokuthuthuka, ngakho-ke ikude kancane. Noma kunjalo, ithembisa amandla esidakamizwa esiphuzwayo esinobuthi obuncane, uma bukhona, be-amphotericin B.         

I-ATI-2307

I-ATI-2307 isesigabeni sokuqala sokukhula futhi iyisidakamizwa esisha se-antifungal esinomshini wokusebenza oyingqayizivele. I-ATI-2307 ivimbela ukusebenza kwe-mitochondrial (i-mitochondria yizakhiwo ezingaphakathi kwamangqamuzana aguqula ukudla kube amandla), inciphisa ukukhiqizwa kwe-ATP (adenosine triphosphate), okuyi-molecule ethwala amandla, okuholela ekuvimbeleni ukukhula.

Njengoba kushiwo ngaphambili, i-ATI-2307 isesigabeni sokuqala. Noma kunjalo, abacwaningi baphothule izifundo ezintathu zomtholampilo zeSigaba 1 ezibonise ukuthi yayibekezelelwa kahle kubantu emazingeni omthamo wokwelapha okulindelekile. Ngakho, indima yomtholampilo ye-ATI-2307 ayicacile; Nokho, umsebenzi wayo obanzi we-in vitro ngokumelene nenqwaba yamagciwane abalulekile esikhunta, okuhlanganisa nezinto eziphilayo ezimelana nezidakamizwa eziningi, kungase kuhumushele indima ebalulekile yale nhlanganisela, ikakhulukazi ezifweni zesikhunta ngenxa yezinto eziphilayo ezimelana nezidakamizwa njengezinhlobo ze-Aspergillus ezimelana ne-azole.