Medicinal Chemistry of Annonaceous Acetogenins: Design, Synthesis, and Biological Evaluation of Novel Analogues

Kojima, Naoto; Tanaka, Tetsuaki

doi:10.3390/molecules14093621

Cited by 85 publications

(36 citation statements)

References 120 publications

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“…Beberapa peneliti menduga bahwa senyawa acetogenin (Squamocin A, B, C dan D) dan annotemoyin 1 and 2 dari daun sirsak yang mempunyai aktivitas sitotoksik (Padma et al, 2009;Yang et al, 2009). Acetogenin ini menghambat NADH-ubiquinon oksidoreduktase (komplek I) pada mitokondria dan menghambat produksi ATP sehingga menyebabkan apoptosis (Morre et al, 1995;Kojima & Tanaka, 2009). Efek sitotoksik pada penelitian ini dengan menggunakan sel vero (sel ginjal normal) terutama dengan konsentrasi tinggi bertentangan dengan penelitian Anne-Isabelle et al, (1997) yang menyebutkan acetogenin ini sangat selektif, hanya menyerang sel kanker yang mempunyai banyak ATP dan senyawa ini tidak menyerang sel normal.…”

Section: Latar Belakangunclassified

Riset Sitotoksik Campuran Ekstrak Daun Sirsak (Annona muricata L) dan Kulit Buah Manggis (Garcinia mangostana L) pada Sel Vero dan AML12

Mardja¹,

Rahmi²,

Rusmawati³

et al. 2016

J. Trop. Pharm. Chem.

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ABSTRAKCampuran Daun sirsak dan Kulit buah manggis sekarang ini banyak digunakan sebagai fitoterapi penyakit kanker dan antioksidan. Tetapi penggunaan bahan ini belum diketahui data keamanannya. Tujuan dilakukan penelitian adalah untuk mengetahui efek sitotoksik campuran ekstrak daun sirsak dan kulit buah manggis terhadap sel vero dan sel AML12. Uji sitotoksik dapat memprediksi keberadaan senyawa yang bersifat toksik secara in vitro menggunakan sel normal atau sel yang telah mengalami transformasi. Uji ini menggunakan 2 jenis cell line, yaitu sel vero dan sel AML12. Sampel berupa simplisia daun sirsak dan kulit buah manggis yang dibuat ekstrak dengan menggunakan etanol 96%. Konsentrasi uji yang digunakan adalah 100; 50; 25; 12,5; 6,25 dan 3,125 g/mL untuk sel vero dan 500; 250; 125; 62,5; 31,25 dan 15,625 g/mL untuk sel AML12. Kultur sel dilakukan di wellplate 96 diinkubasi didalam inkubator CO2 pada suhu 37C selama 24 jam kemudian ditambahkan sampel uji dan selanjutnya diinkubasi kembali didalam inkubator CO2 pada suhu 37C selama 24 jam. Langkah selanjutnya uji MTT dan kemudian dibaca dengan ELISA reader pada panjang gelombang 570nm. Diperoleh hasil sebagai berikut: IC50 55,97 g/mL pada sel vero, dan 43,292 g/mL pada sel AML12. Kesimpulannya sampel campuran ekstrak daun sirsak dan kulit buah manggis ini mempunyai efek toksik terhadap sel vero dan sel AML12 (IC50100 g/mL).Kata kunci: Sitotoksik, Daun sirsak, Kulit buah manggis, sel vero, sel AML12, IC50 ABSTRACTMix of soursop leaves and mangosteen pericarp use as cancer phytotherapy and antioxidant, but it is not yet known its toxicities data. The aim of this study was evaluate cytotoxicity effect of mix of soursop leaves and mangosteen pericarps extract on vero cells and AML12 cells. Toxicity study is one ways to predict the presence of toxic compounds using normal cells or cells that have undergone a transformation. That study was using vero cell and AML12. Samples was ethanolic extract of soursop leaves and mangosteen pericarp. The test dose were 100; 50; 25; 12,5; 6,25 dan 3,125 g/mL in vero cell and 500; 250; 125; 62,5; 31,25 dan 15,625 g/mL in AML12. Cells were cultured in well plate 96 and incubated in CO2, temperature 37C for 24 hours and then added samples and incubated incubated in CO2, temperature 37C for 24 hours. Cell was added MTT and read with ELISA reader. The results showed IC50 55,97g/mL in vero cells and 43,292 g/mL in AML12. Conclusion of

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Section: Latar Belakangunclassified

Riset Sitotoksik Campuran Ekstrak Daun Sirsak (Annona muricata L) dan Kulit Buah Manggis (Garcinia mangostana L) pada Sel Vero dan AML12

Mardja¹,

Rahmi²,

Rusmawati³

et al. 2016

J. Trop. Pharm. Chem.

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“…However, the compounds that can be obtained from the seeds of the Annonaceous acetogenins (ACGs) possess exciting antihelminthic properties, as well as in vivo or in vitro counter-neoplastic properties and antimalarial, antimicrobial and pesticidal activities. They are promising alternatives for antitumor and pesticidal chemotherapy (Bermejo et al, 2005;Kojima and Tanaka, 2009;McLaughlin, 2008). This research explores the use of the discarded seeds for the fabrication of antitumor medicines.…”

Section: Introductionmentioning

confidence: 99%

Three cytotoxic Annonaceous acetogenins from the seeds of Annona squamosa

Miao

Shi

et al. 2016

Phytochemistry Letters

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“…Members of this family of secondary metabolites are often highly cytotoxic displaying sub-nanomolar activity towards human cancer cell lines. 14 …”

Section: Introductionmentioning

confidence: 99%

Simplifying nature: Towards the design of broad spectrum kinetoplastid inhibitors, inspired by acetogenins

Gould

King

Menzies

et al. 2017

Bioorganic & Medicinal Chemistry

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The need for new treatments for the neglected tropical diseases African sleeping sickness, Chagas disease and Leishmaniasis remains urgent with the diseases widespread in tropical regions, affecting the world's very poorest. We have previously reported bis-tetrahydropyran 1,4-triazole analogues designed as mimics of the annonaceous acetogenin natural product chamuvarinin, which maintained trypanocidal activity. Building upon these studies, we here report related triazole compounds with pendant heterocycles, mimicking the original butenolide of the natural product. Analogues were active against T. brucei, with a nitrofuran compound displaying nanomolar trypanocidal activity. Several analogues also showed strong activity against T. cruzi and L. major. Importantly, select compounds gave excellent selectivity over mammalian cells with a furan-based analogue highly selective while remaining active against all three cell lines, thus representing a potential lead for a new broad spectrum kinetoplastid inhibitor.

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Medicinal Chemistry of Annonaceous Acetogenins: Design, Synthesis, and Biological Evaluation of Novel Analogues

Cited by 85 publications

References 120 publications

Riset Sitotoksik Campuran Ekstrak Daun Sirsak (Annona muricata L) dan Kulit Buah Manggis (Garcinia mangostana L) pada Sel Vero dan AML12

Riset Sitotoksik Campuran Ekstrak Daun Sirsak (Annona muricata L) dan Kulit Buah Manggis (Garcinia mangostana L) pada Sel Vero dan AML12

Three cytotoxic Annonaceous acetogenins from the seeds of Annona squamosa

Simplifying nature: Towards the design of broad spectrum kinetoplastid inhibitors, inspired by acetogenins

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