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Senyawa Baru Tanaman Parthenolide Anti-Kanker

Racikan senyawa kimia tanaman-kebun berbunga (feverfew) memiliki sifat anti-kanker yang dapat membunuh sel-sel kanker. Begitu hasil riset lab Dr. Angelo Agathanggelou dari Institute of Cancer and Genomic Studies pada University of Birmingham di Inggris dan koleganya. Riset kolaborasi lintas-disiplin para ahli itu mengekstrak senyawa dari bunga dan memodifikasinya agar dapat memiliki sifat-sifat obat membunuh sel-sel leukemia limfositik kronis (chronic lymphocytic leukaemia/CLL) di lab riset tim peneliti itu. Hasil riset ini dirilis oleh jurnal MedChemComm, edisi Januari 2019 (Li, et al, “Derivatisation of parthenolide to address chemoresistant chronic lymphocytic leukaemia”, MedChemComm, January 28, 2019).

“There are several effective treatments for CLL, but after a time the disease in some patients becomes resistant. We were interested in finding out more about the potential of parthenolide. With expertise from colleagues in the School of Chemistry we've been able to demonstrate that this compound shows real promise and could provide alternative treatment options for CLL patients,” papar Dr. Angelo Agathanggelou, perintis riset ini khususnya chronic lymphocytic leukaemia (CLL). (University of Birmingham, 31/7/2019).

Tim peneliti asal University of Birmingham itu khusus meneliti senyawa parthenolide. Hasil identifikasi para ilmuwan selama ini menemukan bahwa senyawa ini memiliki sifat anti-kanker. Parthenolide adalah produk alamiah yang memiliki aktivitas anti-leukimia. Namun, pemanfaatan klinisnya terbatas karena kurang bioavailabilitas. Maka tim ahli itu meneliti cara jenis senyawa ini dapat diekstrak dari feverfew, tumbuh dan diderivasi.

“Feverfew is a short lived perennial plant which we sowed on an annual basis for the trial to ensure continuity of supply. This was necessary as winter weather can result in plant losses,” ungkap Abigail Gulliver, Horticultural Adviser pada Winterbourne Botanic Garden, University of Birmingham, di Inggris. (University of Birmingham, 31/7/2019)

Hasilnya, tim peneliti itu membuat turunan baru parthenolide dengan bioavailabilitas baik dan properti-properti farmakologis melalui kaskade skrining berbasis aktivitas anti-leukimia in virto dan memperhitungkan sifat-sifat ‘kemiripan-obat’, studi farmakokinetik in virto dan in vivo dan pengujian liabilitas hERG.

“This research is important not only because we have shown a way of producing parthenolide that could make it much more accessible to researchers, but also because we've been able to improve its “drug-like” properties to kill cancer cells. It's a clear demonstration that parthenolide has the potential to progress from the flowerbed into the clinic,” ungkap Profesor John Fossey dari School of Chemistry pada University of Birmingham. (University of Birmingham, 31/7/2019)

Studi-studi in virto tim ahli itu menunjukkan hasil aktivitas senyawa anti-leukimia yang sebanding dengan DMAPT—turunan parthenolide sebelumnya. Senyawa baru itu memperlihatkan kemampuan pro-oksidan. Sehingga tim ahli asal University of Birmingham dapat langsung memproduksi parthenolide dari tanaman guna menghasilkan sejumlah senyawa pembunuh sel kanker dalam percobaanin virto.

Sifat khusus senyawa parthenolide antara lain meningkatkan kadar spesies oksigen reaktif (oxygen species/ROS) dalam sel-sel. Sel-sel kanker sudah memiliki tingkat yang lebih tinggi dari molekul-molekul yang tidak stabil ini sehingga efek parthenolide adalah meningkatkan level-level ini ke titik kritis, menyebabkan sel mati.

Proyek riset itu merupakan studi multi-disiplin yang melibatkan banyak ahli dari Institute of Cancer and Genomic Studies pada University of Birmingham,  School of Chemistry dan perusahan-perusahan  jasa riset obat, Sygnature Discovery dan Apconix, dan Winterbourne Botanic Garden dari University of Birmingham yang mengawasi penanaman tananam-tanamannya dengan volume cukup bagi skrening obat. Lee Hale, Kepala Winterbourne Botanic Garden dan Abigail Gulliver, Horticultural Adviser pada Winterbourne mengawasi penanaman dan panen tanaman-tanamannya.

“After trials on related plant species within the Asteraceae family it soon became apparent that Tanacetum parthenium - feverfew - provided the optimum levels of parthenolide,” ungkap Lee Hale dari Winterbourne Botanic Garden, University of Birmingham, 58 Edgbaston Park Road, Edgbaston, Birmingham, Inggris. (University of Birmingham, 31/7/2019)

Ahli-ahli peneliti yang terlibat dalam proyek riset itu ialah (1) Xingjian Li asal School of Chemistry, University of Birmingham, Edgbaston, Birmingham, Inggris; (2) Daniel T. Payne asal School of Chemistry, University of Birmingham, Edgbaston, Birmingham, Inggris; (3) Badarinath Ampolu asal Sygnature Discovery, The Discovery Building, BioCity, Pennyfoot Street, Nottingham, Inggris;

(4) Nicholas Bland asal Sygnature Discovery, The Discovery Building, BioCity, Pennyfoot Street, Nottingham, Inggris; (5) Jane T. Brown asal Sygnature Discovery, The Discovery Building, BioCity, Pennyfoot Street, Nottingham, Inggris; (6) Mark J. Dutton asal School of Chemistry, University of Birmingham, Edgbaston, Birmingham, Inggris;

(7) Catherine A. Fitton asal Institute for Cancer and Genomic Sciences, University of Birmingham, Edgbaston, Birmingham, Inggris; (8) Abigail Gulliver asal Winterbourne Botanic Garden, University of Birmingham, 58 Edgbaston Park Road, Edgbaston, Birmingham, Inggris; (9) Lee Hale asal Winterbourne Botanic Garden, University of Birmingham, 58 Edgbaston Park Road, Edgbaston, Birmingham, Inggris;

(10)  Daniel Hamza asal Sygnature Discovery, The Discovery Building, BioCity, Pennyfoot Street, Nottingham, Inggris; (11) Geraint Jones asal Sygnature Discovery, The Discovery Building, BioCity, Pennyfoot Street, Nottingham, Inggris: (12) Rebecca Lane asal Sygnature Discovery, The Discovery Building, BioCity, Pennyfoot Street, Nottingham, Inggris;

(13) Andrew G. Leach asal School of Pharmacy and Biomolecular Sciences, Liverpool John Moores University, Byrom Street, Liverpool, Inggris: (14) Louise Male asal X-Ray Crystallography Facility, School of Chemistry, University of Birmingham, Edgbaston, Birmingham, Inggris: (15) Elena G. Merisor asal Sygnature Discovery, The Discovery Building, BioCity, Pennyfoot Street, Nottingham, Inggris;

(16) Michael J. Morton asal ApconiX Ltd, Alderly Park, Nether Alderly, Cheshire, Inggris: (17) Alex S. Quy asal School of Chemistry, University of Birmingham, Edgbaston, Birmingham, Inggris: (18) Ruth Roberts asal  ApconiX Ltd, Alderly Park, Nether Alderly, Cheshire, Inggris dan School of Biosciences, University of Birmingham, Edgbaston, Birmingham, Inggris;

(19) Rosanna Scarll asal Institute for Cancer and Genomic Sciences, University of Birmingham, Edgbaston, Birmingham, Inggris; (20) Timothy Schulz-Utermoehl asal Sygnature Discovery, The Discovery Building, BioCity, Pennyfoot Street, Nottingham, Inggris; (21) Profesor Tatjana Stankovic asal Institute for Cancer and Genomic Sciences, University of Birmingham, Edgbaston, Birmingham, Inggris: (22) Brett Stevenson asal Sygnature Discovery, The Discovery Building, BioCity, Pennyfoot Street, Nottingham, Inggris.

 

 

 

Oleh: Servas Pandur