Niclosamide ọ bụ ọgwụ nje?

Niclosamide bụ ihe na-adọrọ adọrọ nke dọtara mmasị dị ukwuu na mpaghara ahụike n'ihi ngwa dị iche iche. Agbanyeghị, a na-enwekarị mgbagwoju anya gbasara nhazi ya na akụrụngwa ya. Iji lebara nke a anya, ka anyị banye n'ime ọdịdị nke Niclocide ntụ ntụ ma nyochaa ọrụ ya na nkà mmụta ọgwụ ọgbara ọhụrụ.

Niclosamide abụghị ọgwụ nje n'echiche ọdịnala. Ọ bụ nke otu ọgwụ a maara dị ka anthelmintics, bụ nke a na-ejikarị agwọ ọrịa worm parasitic. N'agbanyeghị nkewa nke a, nchọpụta na nso nso a egosila na niclosamide nwere ọtụtụ ihe omume dị ndụ, gụnyere antiviral, anticancer, na mmetụta metabolic. Ntughari nke a ebutela mmasị n'ịmeghachi niclosamide maka ọnọdụ ahụike dị iche iche gafere na mbụ e bu n'obi were ya.

Gịnị bụ Niclosamide eji agwọ ọrịa?

Niclosamide nwere ogologo akụkọ ihe mere eme nke iji ma mmadụ na ọgwụgwọ anụmanụ. Ngwa ya bụ isi bụ n'ịgwọ ọrịa tapeworm, ọrụ ọ rụzuru nke ọma ruo ọtụtụ iri afọ. Ọgwụ ahụ na-arụ ọrụ site na itinye aka na metabolism ike nke tapeworms, n'ikpeazụ na-eduga na ọnwụ ha na ịchụpụ ha n'ahụ onye ọbịa.

Agbanyeghị, akụkọ niclosamide akwụsịghị na nje nje. N'afọ ndị na-adịbeghị anya, ndị nchọpụta achọpụtala plethora nke enwere ike iji ya mee ihe maka ogige a dị iche iche. Otu akụkụ nwere mmasị bụ ọrụ ya megide nje nje dị iche iche. Nnyocha egosila na niclosamide na-egosipụta ihe mgbochi nje dị iche iche, na-egosipụta nrụpụta ọrụ megide nje dị ka SARS-CoV-2 (nje virus na-ahụ maka COVID-19), influenza, Zika, na ahụ ọkụ dengue.

Aghọtaghị nke ọma usoro nke niclosamide na-egosipụta mmetụta mgbochi ya, mana ekwenyere na ọ gụnyere ọtụtụ ụzọ. Dịka ọmụmaatụ, ọ nwere ike igbochi mmegharị nje virus site na itinye aka na usoro cellular nke nje na-ejide maka mmepụta nke ha. Na mgbakwunye, egosila niclosamide ka ọ na-agbanwe nzaghachi sel ndị ọbịa, nwere ike ịkwalite ihe nchebe nke anụ ahụ megide ọrịa nje.

Na mgbakwunye na ihe mgbochi ya, Niclocide ntụ ntụ egosila nkwa na ngalaba nke oncology. Ọtụtụ nchọpụta egosila mmetụta ya na-egbochi ọrịa kansa megide ụdị ụbụrụ dị iche iche, gụnyere colorectal, ara, prostate, na ọrịa cancer akpa ume. Ọgwụ a na-egosi na ọ na-arụ ọrụ site n'ọtụtụ usoro, dị ka igbochi mgbasa mkpụrụ ndụ cancer, na-ebute apoptosis (ọnwụ cell emepụtara), na igbochi mkpụrụ ndụ mkpụrụ ndụ kansa.

Kedu ka niclosamide ntụ ntụ si arụ ọrụ?

Niclosamide ntụ ntụ, ihe na-arụsi ọrụ ike n'ime ọgwụ anthelmintic dị iche iche, na-arụ ọrụ site na usoro mgbagwoju anya nke na-elekwasị anya n'ụdị nje parasitic mana na-emetụtakwa usoro cellular dị iche iche na mpaghara ndị ọzọ. Ịghọta otú niclosamide ntụ ntụ si arụ ọrụ dị oké mkpa maka inwe ekele maka ike ya na ngwa ndị nwere ike na mpaghara ahụike dị iche iche.

N'isi ya, usoro niclosamide na-arụ ọrụ gụnyere ịkpaghasị mmepụta ike na sel ndị e lekwasịrị anya. N'ihe gbasara ojiji izizi ya megide tapeworms, niclosamide na-egbochi phosphorylation oxidative, usoro bụ isi na iku ume cellular. Kpọmkwem, ọ na-arụ ọrụ dị ka protonophore, nke pụtara na ọ nwere ike ibu proton n'ofe cell membranes. Omume a na-akpaghasị proton gradient dị mkpa maka njikọ ATP, na-agụ agụụ nke parasaiti ike nke ọma.

Nkwụsị nke metabolism ike ejedebeghị na nje nje, Otú ọ dị. Otu usoro a na-enye aka na nrụpụta niclosamide megide mkpụrụ ndụ kansa, nke na-agbanwekarị profaịlụ metabolic ma e jiri ya tụnyere sel nkịtị. Site na itinye aka na ọrụ mitochondrial, niclosamide nwere ike ịhọrọ mkpụrụ ndụ kansa nke na-adabere na phosphorylation oxidative maka mmepụta ume.

Na mgbakwunye na mmetụta ya na metabolism ike, a chọpụtala niclosamide na-emegharị ọtụtụ ụzọ akara ekwentị dị mkpa. Otu n'ime ihe kachasị mkpa bụ ikike ya igbochi ụzọ akara Wnt/β-catenin. Ụzọ a na-arụ ọrụ dị oke mkpa n'ịbawanye sel, dị iche iche, na nlekọta sel stem. Site na ikpuchi akara Wnt, niclosamide nwere ike igbochi uto na nlanarị mkpụrụ ndụ kansa, ọkachasị ndị dabere n'ụzọ a maka mmụba ha.

A na-eche na ihe antiviral nke Niclosamide sitere na ọtụtụ usoro. Otu akụkụ dị mkpa bụ ikike ya iji wepụ pH endosomal. Ọtụtụ nje na-achọ gburugburu acidic na endosomes maka ịbanye nke ọma n'ime sel ndị ọbịa. Site n'ịmepụta akụkụ ndị a, niclosamide nwere ike igbochi njikọ nje na ntinye. Na mgbakwunye, egosiri na niclosamide na-egbochi mmeghari nke ụfọdụ nje site na igbochi protein nje a kapịrị ọnụ ma ọ bụ site n'ịgbanwe ụzọ sel ndị ọbịa nke nje na-erigbu maka mmụgharị ha.

Mmetụta mgbochi mkpali nke Niclocide ntụ ntụ Ejikọtara ya na ikike ya igbochi ụzọ mgbaàmà STAT3. STAT3 bụ ihe ntụgharị ederede na-arụ ọrụ dị mkpa na mbufụt na nzaghachi mgbochi. Site na ịkwụsị ọrụ STAT3, niclosamide nwere ike belata mmepụta nke cytokines pro-inflammatory ma nwee ike ibelata ọnọdụ mkpali.

N'ihe gbasara ọrịa metabolic, mmetụta niclosamide na metabolism ike na-agbatị karịa nkwụsịtụ dị mfe. Achọpụtara ya ka ọ rụọ ọrụ AMP-activated protein kinase (AMPK), isi ihe na-achịkwa homeostasis ume cell. Ịgbalite AMPK nwere ike ibute mmụba glucose na-abawanye, mmụba insulin na-enwe mmetụta, yana imeziwanye metabolism lipid, nke niile bara uru na ọgwụgwọ ọrịa metabolic dị ka ụdị ọrịa shuga 2 na oke ibu.

Ike neuroprotective nke niclosamide bụ mpaghara nyocha na-aga n'ihu. Ụfọdụ ọmụmụ na-atụ aro na ọ nwere ike ichebe neurons site na ibelata nrụgide oxidative na mbufụt, isi ihe abụọ dị na ọrịa neurodegenerative. Ọzọkwa, ikike ya ịgbanwe metabolism ike sel nwere ike ịba uru n'ịkwado ahụike na ọrụ neuronal.

Ọ dị mkpa ịmara na ọ bụ ezie na niclosamide ntụ ntụ gosipụtara nkwa na ngwa ndị a dị iche iche, arụmọrụ ya nwere ike imetụta ihe ndị dị ka bioavailability na nkesa anụ ahụ. Ụdị ntụ ntụ nke niclosamide adịghị etinye aka na ya mgbe a na-ewere ya n'ọnụ, nke mere ka ndị nchọpụta nyochaa usoro ndị ọzọ na ụzọ nnyefe iji mee ka ọ dị irè n'ịgwọ ọnọdụ usoro.

N'ikpeazụ, niclosamide ntụ ntụ na-arụ ọrụ site na usoro ọrụ dị iche iche nke na-agbatị karịa ihe mbụ e ji mee ihe dị ka onye na-ahụ maka anthelmintic. Ikike ya igbanwe metabolism ike, ụzọ akara ekwentị, yana usoro ndu ndị ọzọ dị iche iche na-eme ka ọ bụrụ ngwakọta dị iche iche nwere ngwa nwere ike gafee ọtụtụ ọnọdụ ahụike. Ka nyocha na-aga n'ihu, nghọta anyị banyere otu niclosamide si arụ ọrụ nwere ike gbasaa, nwere ike imepe ụzọ ọhụrụ maka ọgwụgwọ ya.

Niclosamide nwere ike igbu nje bacteria?

Ajụjụ nke ma niclosamide nwere ike igbu nje bacteria bụ ihe na-adọrọ mmasị, karịsịa n'ihi na ogige ahụ na-arụ ọrụ nke ọma megide nje nje na ike ya na-apụta megide nje na mkpụrụ ndụ kansa. Mgbe Niclocide ntụ ntụ akọwapụtaghị ya dị ka ọgwụ nje n'echiche ọdịnala, nchọpụta egosila na o nwere ụfọdụ ihe na-egbu nje, na-agbakwụnye akụkụ ọzọ n'ọtụtụ ihe omume ndụ ya na-adọrọ mmasị.

A hụla mmetụta antibacterial nke Niclosamide na nyocha dị iche iche, ọ bụ ezie na ọ dị mkpa ịmara na ike ya na ụdị ọrụ dị iche iche nke nje bacteria dị iche na nke ọgwụ nje. A na-eche na usoro nke niclosamide na-egosipụta mmetụta nje ya nwere njikọ na ikike ọ nwere imebi mmepụta ume cell na ikike akpụkpọ ahụ, yiri ihe ọ na-eme megide nje nje.

Otu n'ime ihe nchoputa kachasị dị ịrịba ama gbasara ihe ndị na-egbu nje niclosamide bụ ọrụ ya megide Pseudomonas aeruginosa, nje bacteria siri ike na-agwọ ọrịa mara maka nkwụsị nke ọgwụ nje. Nnyocha egosiwo na niclosamide nwere ike igbochi uto nke P. aeruginosa na ọbụna welie irè nke ụfọdụ ọgwụ nje mee ihe mgbe ejikọtara ya. Mmetụta synergistic a na-ekwe nkwa n'ihu na-abawanye ụba nke ọgwụ nje, n'ihi na ọ na-egosi na enwere ike iji niclosamide mee ka ọ dịghachi irè nke ọgwụ nje ndị dị ugbu a.

Ọzọkwa, niclosamide egosipụtawo ọrụ megide nje bacteria ndị ọzọ metụtara ụlọ ọgwụ. Nnyocha egosiwo na ọ dị irè megide Staphylococcus aureus, gụnyere methicillin-resistant strains (MRSA), nke bụ isi nchegbu na ntọala ahụike n'ihi na ha na-eguzogide ọtụtụ ọgwụ nje. Ikike Niclosamide nwere ịlụso ụdị ọgụ ndị a ọgụ na-egosipụta ike ya dị ka ngwá ọrụ n'ọgụ a na-alụso nje na-eguzogide ọgwụ nje.

Akụkụ ọzọ na-adọrọ mmasị nke ọrụ antibacterial nke niclosamide bụ mmetụta ya na biofilms nje bacteria. Biofilms bụ obodo nke nje bacteria na-arapara n'elu elu ma tinye ya na matriks extracellular emepụtara onwe ya. Ihe owuwu ndị a na-esikarị ike ikpochapụ ma na-atụnye ụtụ nke ukwuu n'ịnọgidesi ike nke nje na-efe efe. Nnyocha egosiwo na niclosamide nwere ike imebi nhazi biofilm na ụdị nje bacteria dị iche iche, gụnyere P. aeruginosa na S. aureus. Ikike a iledo ihe nkiri biofilms na-ewepụta niclosamide iche na ọtụtụ ọgwụ nje ọdịnala ma nwee ike mee ka ọ baa uru n'ịgwọ ọrịa na-adịghị ala ala ma ọ bụ nke metụtara ngwaọrụ.

Ngwongwo antibacterial nke Niclosamide na-agafe karịa igbu mmadụ ma ọ bụ igbochi nje bacteria. Nnyocha e mere egosiwo na ọ pụkwara imetụta nje nje bacteria, nke na-ezo aka n'ikike nje bacteria na-ebute ọrịa. Dịka ọmụmaatụ, achọpụtara na niclosamide na-egbochi mmepụta nke ụfọdụ ihe na-akpata nje na P. aeruginosa, nke nwere ike ibelata ikike nje ahụ nwere ike imerụ onye ọbịa ahụ.

Na ngwụcha, Niclocide ntụ ntụ bụ ngwakọta nwere ọtụtụ akụkụ nke, ọ bụ ezie na ọ bụghị ọgwụ nje n'echiche ọdịnala, nwere ọtụtụ ihe omume dị ndụ. Ojiji izizi ya dị ka onye na-ahụ maka anthelmintic agbasawanyela itinye ngwa nwere ike na ọgwụgwọ antiviral, ọgwụgwọ ọrịa kansa, yana njikwa nsogbu metabolic. Ntughari nke niclosamide, yana profaịlụ nchekwa ya dị ogologo, na-eme ka ọ bụrụ onye na-atọ ụtọ maka mbọ ịghaghachi ọgwụ. Ka nyocha na-aga n'ihu, anyị nwere ike ịhụ niclosamide na-apụta dị ka ngwá ọrụ bara uru n'ịgwọ ọnọdụ ahụike dịgasị iche iche karịa iji ya mee ihe mbụ.

Ọ bụrụ na ị nwekwara mmasị na ngwaahịa a ma chọọ ịmatakwu nkọwa ngwaahịa, ma ọ bụ chọọ ịmata maka ngwaahịa ndị ọzọ metụtara, biko nweere onwe gị ịkpọtụrụ. iceyqiang@aliyun.com.

References:

1. Xu, J., Shi, PY, Li, H., & Zhou, J. (2020). Broad Spectrum Antiviral Agent Niclosamide na ike ọgwụgwọ ya. Ọrịa na-efe efe ACS, 6 (5), 909-915.

2. Chen, W., Mook, RA, Premont, RT, & Wang, J. (2018). Niclosamide: E wezụga ọgwụ antihelminthic. Nrịbama ekwentị, 41, 89-96.

3. Mostafa, A., Kandeil, A., Elshaier, YAMM, Kutkat, O., Moatasim, Y., Rashad, AA, ... & Ali, MA (2020). Ọgwụ FDA kwadoro nke nwere ike in vitro antiviral ọrụ megide nnukwu ọrịa iku ume coronavirus 2. Pharmaceuticals, 13(12), 443.

4. Kadri, H., Lambourne, OA, & Mehellou, Y. (2018). Niclosamide, ọgwụ nwere ọtụtụ ebumnuche (re). ChemMedChem, 13 (11), 1088-1091.

5. Mook, RA, Wang, J., Ren, XR, Chen, M., Spasojevic, I., Barak, LS, ... & Chen, W. (2015). Ihe omumu ihe omumu nke Wnt/β-catenin inhibition na Niclosamide chemotype: Nchọpụta ihe ndị na-emepụta ihe na mkpughe ọgwụ ka mma. Bioorganic & ọgwụ Chemistry, 23(17), 5829-5838.

6. Jurgeit, A., McDowell, R., Moese, S., Meldrum, E., Schwendener, R., & Greber, UF (2012). Niclosamide bụ onye na-ebu proton ma na-ezubere endosomes acidic nwere nnukwu mmetụta mgbochi nje. Ọrịa PLoS, 8 (10), e1002976.

7. Tao, H., Zhang, Y., Zeng, X., Shulman, GI, & Jin, S. (2014). Niclosamide ethanolamine na-ebute obere mitochondrial uncoupling na-eme ka mgbaàmà ọrịa shuga dị na ụmụ oke. Ọgwụ okike, 20 (11), 1263-1269.

8. Pearson, RD, Hewlett, EL (1985). Niclosamide ọgwụgwọ maka ọrịa tapeworm. Akwụkwọ akụkọ nke ọgwụ ime ime, 102(4), 550-551.

9. Imperi, F., Massai, F., Ramachandran Pillai, C., Longo, F., Zennaro, E., Rampioni, G., ... & Leoni, L. (2013). Ndụ ọhụrụ maka ọgwụ ochie: ọgwụ anthelmintic niclosamide na-egbochi Pseudomonas aeruginosa quorum nghọta. Ndị na-ahụ maka ọgwụ nje na Chemotherapy, 57(2), 996-1005.

10. Rajamuthiah, R., Fuchs, BB, Conery, AL, Kim, W., Jayamani, E., Kwon, B., ... & Mylonakis, E. (2015). Ịmeghachi ọgwụ anthelmintic salicylanilide iji lụso Staphylococcus aureus na-eguzogide ọgwụ. PLoS Otu, 10 (4), e0124595.