Studi In Silico Potensi Metabolit Sekunder Eleutherine palmifolia (L.) Merr. sebagai Inhibitor Protein E6 dan E7 dari Human Papilloma Virus

Abstract—Human Papilloma Virus (HPV), especially variants 16 and 18, are the causative agents of cervicals cancer. The E6 and E7 proteins are known to play a role in the cervical cancer regulation. Dayak onion plants have been widely used by local people as traditional medicine, including in treating cancer. Until now, there is no known compound or scientific evidence related to its activity of Dayak onion plants against HPV. The plant contains flavonoids, alkaloids, naphtoquinone and several types of polyphenols. Several flavonoids and naphtoquinones from other plants are known to have the ability to treat cancer, especially cervical cancer. In this study, we performed in silico screening of the secondary metabolites, especially the flavonoid and naphtoquinone groups, of Dayak onions which might be active against E6 and E7 proteins of HPV16 and 18. The result showed that there were six flavonoids’ compounds and four naphtoquinone compounds which were predicted as candidates to treat cervical cancer. The Pa values of all compounds, including the positive control, the resveratrol, were less than 0.5 which meant that all compounds showed no activity as anticancer. Analysis of physicochemical, pharmacokinetics, and toxicity predictions exhibited that all compounds could be absorbed, distributed, metabolized, and excreted in human body and non-toxic. Among the ten compounds, only 1,4-Naphthoquinone had weaker interaction with E6 and E7 proteins than resveratrol. Ephicatecin gallate had the strongest binding affinity with protein E6 HPV16 (-7,7 kkal.mol-1) and E7 HPV18 (-7,1 kkal.mol-1), whilst rutin was the strongest interaction with E6 HPV16 (-7,8 kkal.mol-1) and E7 HPV18 (-6,2 kkal.mol-1). As a conclusion, the ephicatecin gallate and rutin compounds of BDayak onion could be used as potent candidat to inactivate the E6 and E7 proteins of HPV 16 and HPV18. The two compounds were also predicted had similarity as medicine and were suitable in bioavailability to be applied as agents for cervical cancer therapy. Keywords: E6 and E7 oncogene proteins, cervical cancer, flavonoid, naphtoquinone, onion dayak   Abstrak—Human Papiloma Virus (HPV) varian tipe 16 dan 18 merupakan salah satu penyebab kanker serviks. Protein E6 dan E7 dari HPV merupakan protein utama yang berperan dalam regulasi kanker servix. Tanaman Bawang Dayak telah banyak digunakan secara tradisional untuk mengatasi kanker. Hingga saat ini belum diketahui senyawa atau pembuktian ilmiah terkait khasiatnya pada tanaman Bawang Dayak. Bawang Dayak mengandung senyawa flavonoid, alkaloid, naphtoquinone dan beberapa tipe polifenol. Beberapa senyawa golongan flavonoid dan naphtoquinone dari tumbuhan lain telah dibuktikan berperan dalam mengatasi kanker, terutama kanker servix. Pada penelitian ini dilakukan skrining secara in silico metabolit sekunder, khususnya golongan flavonoid dan naphtoquinone, dari Bawang Dayak yang berpotensi menghambat protein E6 dan E7 dari HPV16 dan HPV18. Hasil analisis menunjukkan bahwa ada enam senyawa golongan flavonoid dan dan empat senyawa naphtoquinone yang diduga berpotensi sebagai anti kanker serviks. Nilai Pa kurang dari 0,5 untuk semua metabolit sekunder dan kontrol positif, resveratrol tidak menunjukkan aktivitas. Analisis sifat fisikokimia, farmakokinetik dan potensi toksisitas bagi tubuh menunjukkan bahwa semua senyawa teridentifikasi mampu diabsorbsi, didistribusi, dimetabolisme dan diekskresi dari tubuh dan tidak toksik. Interaksi sepuluh metabolit sekunder Bawang Dayak dengan protein E618 dan E716 menunjukkan bahwa hanya 1,4-Naphthoquinone yang berinteraksi lebih lemah dibandingkan resveratrol. Ephicatecin gallate berinteraksi paling kuat dengan protein E6 HPV16 (-7,7 kkal.mol-1) dan E7 HPV18 (-7,1 kkal.mol-1). Rutin berinteraksi paling baik dengan E6 HPV16 (-7,8 kkal.mol-1) dan E7 HPV18 (-6,2 kkal.mol-1). Berdasarkan hasil analisa, dapat disimpulkan bahwa senyawa ephicatecin gallate dan rutin Bawang Dayak berpotensi sebagai kandidat penghambat protein E6 dan E7 dari HPV 16 dan HPV18. Kedua senyawa juga diduga memiliki kesamaan dengan obat dan secara bioavailibilitasnya cocok jika diterapkan sebagai agen terapi kanker serviks. Kata kunci: bawang dayak, flavonoid, kanker servix, naphtoquinone, protein onkogen E6 dan E

Structural Aspects of Split G-Quadruplexes in Quadruplex-Duplex Hybrid Systems

G-quadruplexes are secondary structures of nucleic acids increasingly employed for biological and also technological applications. Being of particular interest, a structural motif called quadruplex-duplex (QD) hybrid comprises both a G-quadruplex and duplex domain. Here, we attempted to engineer a bimolecular quadruplex-duplex hybrid through dual recognition of a receptor by a target strand with the simultaneous formation of both G-quadruplex and duplex structures. Three different constructs were designed for the G-quadruplex receptor, featuring either one, two, or three vacant sites. Addition of the target strand filled the vacancies when simultaneously hybridizing with flanking sequences to form a duplex as shown by NMR studies. Formed QD hybrid constructs either constitute an 11 : 1, 10 : 2, or 9 : 3 split G-quadruplex system. The 10 : 2 QD construct folds into a non-canonical V-loop topology. Remarkably, the latter also accommodates 5’-overhang residues of the target strand although suggested to impose a steric penalty. Formation of the duplex domain is demonstrated to be critical for the successful formation of the intact G-quadruplex domain. With the formation of a unique QD junction for detection, the constructs may constitute valuable tools for single strand capturing strategies

Studi In Silico Potensi Metabolit Sekunder Eleutherine palmifolia (L.) Merr. sebagai Inhibitor Protein E6 dan E7 dari Human Papilloma Virus

Human Papilloma Virus (HPV), especially variants 16 and 18, are the causative agents of cervicals cancer. The E6 and E7 proteins are known to play a role in the cervical cancer regulation. Dayak onion plants have been widely used by local people as traditional medicine, including in treating cancer. Until now, there is no known compound or scientific evidence related to its activity of Dayak onion plants against HPV. The plant contains flavonoids, alkaloids, naphtoquinone and several types of polyphenols. Several flavonoids and naphtoquinones from other plants are known to have the ability to treat cancer, especially cervical cancer. In this study, we performed in silico screening of the secondary metabolites, especially the flavonoid and naphtoquinone groups, of Dayak onions which might be active against E6 and E7 proteins of HPV16 and 18. The result showed that there were six flavonoids’ compounds and four naphtoquinone compounds which were predicted as candidates to treat cervical cancer. The Pa values of all compounds, including the positive control, the resveratrol, were less than 0.5 which meant that all compounds showed no activity as anticancer. Analysis of physicochemical, pharmacokinetics, and toxicity predictions exhibited that all compounds could be absorbed, distributed, metabolized, and excreted in human body and non-toxic. Among the ten compounds, only 1,4-Naphthoquinone had weaker interaction with E6 and E7 proteins than resveratrol. Ephicatecin gallate had the strongest binding affinity with protein E6 HPV16 (-7,7 kkal.mol-1) and E7 HPV18 (-7,1 kkal.mol-1), whilst rutin was the strongest interaction with E6 HPV16 (-7,8 kkal.mol-1) and E7 HPV18 (-6,2 kkal.mol-1). As a conclusion, the ephicatecin gallate and rutin compounds of BDayak onion could be used as potent candidat to inactivate the E6 and E7 proteins of HPV 16 and HPV18. The two compounds were also predicted had similarity as medicine and were suitable in bioavailability to be applied as agents for cervical cancer therapy. Keywords: E6 and E7 oncogene proteins, cervical cancer, flavonoid, naphtoquinone, onion daya

Biokomposit Hidrogel dengan Ekstrak Centella asiatica sebagai Penutup Luka

Abstract—When wounds occur on skin, cell regeneration and healing process will occur. Imperfect cell regeneration will end up leaving ugly scars. Any open wounds will have a high chance of being infected, further slowing the healing processes. The bacteria involved in wound infection are as follow: Pseudomonas aeruginosa, Escherichia coli and  Staphylococcus aureus. The usage of current medical adhesive to cover wound has many implications: cannot be used multiple times and untuk may end up resulting in MARSI (Medical Adhesive-Related Skin Injuries). To solve those problems, this research aims to find an alternative wound dressing that are able to solve the problems mentioned earlier. The synthesis of biocomposite hydrogel consists of bacterial cellulose mixed with gelatin with the crosslinker agent glutaraldehyde. The mixture is then given the wild herbs Centella asiatica extract as an active ingredient. It has been found that the best formulation consists of using 10% gelatine: bacterial cellulose paste with the ratio 200:1 with the total glutaraldehyde concentration of 1%. Furthermore, Centella asiatica 10% are not able to penetrate the human model skin, and did not exhibit any antimicrobial activity against Escherichia coli, Pseudomonas aeruginosa, and Staphylococcus aureus. Keywords: biocomposite hydrogel, nata de coco, bacterial cellulose, gelatine, centella asiatica extract, wound dressing Abstrak—Ketika luka terjadi pada kulit, regenerasi sel dan proses penyembuhan akan terjadi. Regenerasi sel yang tidak sempurna dapat menghasilkan bekas luka yang kurang enak dipandang. Selain itu, luka terbuka berisiko terinfeksi oleh patogen sehingga penyembuhan akan terhambat. Bakteri yang berperan pada infeksi luka adalah Pseudomonas aeruginosa, Escherichia coli dan Staphylococcus aureus. Penggunaan medical adhesive untuk menutup luka punya banyak kekurangan yaitu penggunaannya tidak bisa dilakukan berulang dan dapat menyebabkan MARSI (Medical Adhesive-Related Skin Injuries), yaitu berbagai komplikasi dan luka pada kulit yang ditempeli dengan produk tersebut. Untuk mengatasi pemasalahan tersebut, penelitian ini bertujuan untuk mendapatkan alternatif penutup luka terbaru yang dapat mengatasi permasalahan yang telah disebutkan. Pembuatan hidrogel biokomposit terdiri dari selulosa bakteri yang direaksikan dengan gelatin menggunakan agen crosslinker glutaraldehida. Campuran kemudian ditambahkan  bahan aktif dari ekstrak tanaman liar Centella asiatica. Didapatkan formulasi terbaik menggunakan perbandingan 10% gelatin:pasta selulosa bakteri = 200:1 dengan konsentrasi total glutaraldehida sebanyak 1%. Selain itu, ekstrak Centella asiatica 10% juga tidak dapat mempenetrasi model kulit manusia, serta tidak memiliki aktivitas antibakteri baik pada Escherichia coli, Pseudomonas aeruginosa, dan Staphylococcus aureus. Kata kunci: hidrogel biokomposit, nata de coco, selulosa bakteri, gelatin, ekstrak centella asiatica, penutup luk

Biokomposit Hidrogel dengan Ekstrak Centella Asiatica sebagai Penutup Luka

When wounds occur on skin, cell regeneration and healing process will occur. Imperfect cell regeneration will end up leaving ugly scars. Any open wounds will have a high chance of being infected, further slowing the healing processes. The bacteria involved in wound infection are as follow: Pseudomonas aeruginosa, Escherichia coli and Staphylococcus aureus. The usage of current medical adhesive to cover wound has many implications: cannot be used multiple times and untuk may end up resulting in MARSI (Medical Adhesive-Related Skin Injuries). This research aims to find an alternative wound dressing that are able to solve the problems mentioned earlier. The synthesis of biocomposite hydrogel consists of bacterial cellulose mixed with gelatin with the crosslinker agent glutaraldehyde. The mixture is then given the wild herbs Centella asiatica extract as an active ingredient. It has been found that the best formulation consists of using 10% gelatine: bacterial cellulose paste with the ratio 200:1 with the total glutaraldehyde concentration of 1%. Furthermore, Centella asiatica 10% are not able to penetrate the human model skin, and did not exhibit any antimicrobial activity against Escherichia coli, Pseudomonas aeruginosa, and Staphylococcus aureus. Ketika luka terjadi pada kulit, regenerasi sel dan proses penyembuhan akan terjadi. Regenerasi sel yang tidak sempurna dapat menghasilkan bekas luka yang kurang enak dipandang. Selain itu, luka terbuka berisiko terinfeksi oleh patogen sehingga penyembuhan akan terhambat. Bakteri yang berperan pada infeksi luka adalah Pseudomonas aeruginosa, Escherichia coli dan Staphylococcus aureus. Penggunaan medical adhesive untuk menutup luka punya banyak kekurangan yaitu penggunaannya tidak bisa dilakukan berulang dan dapat menyebabkan MARSI (Medical Adhesive-Related Skin Injuries), yaitu berbagai komplikasi dan luka pada kulit yang ditempeli dengan produk tersebut. Penelitian ini bertujuan untuk mendapatkan alternatif penutup luka terbaru yang dapat mengatasi permasalahan yang telah disebutkan. Pembuatan hidrogel biokomposit terdiri dari selulosa bakteri yang direaksikan dengan gelatin menggunakan agen crosslinker glutaraldehida. Campuran kemudian ditambahkan bahan aktif dari ekstrak tanaman liar Centella asiatica. Didapatkan formulasi terbaik menggunakan perbandingan 10% gelatin:pasta selulosa bakteri = 200:1 dengan konsentrasi total glutaraldehida sebanyak 1%. Selain itu, ekstrak Centella asiatica 10% juga tidak dapat mempenetrasi model kulit manusia, serta tidak memiliki aktivitas antibakteri baik pada Escherichia coli, Pseudomonas aeruginosa, dan Staphylococcus aureus