Design and Molecular Docking Study of Antimycin A&amp;lt;sub&amp;gt;3&amp;lt;/sub&amp;gt; Analogues as Inhibitors of Anti-Apoptotic Bcl-2 of Breast Cancer

Arsianti, Ade; Fadilah, Fadilah; Kusmardi,; Tanimoto, Hiroki; Morimoto, Tsumoru; Kakiuchi, Kiyomi

doi:10.4236/ojmc.2014.43006

Cited by 10 publications

(6 citation statements)

References 14 publications

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“…Ravi and Ragunathan (2016) conducted in silico analysis of alien and microdontin with P. falciparum calcium-dependent protein kinase [18]. In 2014, we conducted in silico molecular docking study on antimycin A analogs as inhibitors of antiapoptotic Bcl-2 of breast cancer [19]. Recently, In 2016, we have reported in silico molecular docking studies of opened-chain analogs of antimycin A 3 as caspases inhibitors of apoptosis in colorectal cancer [20].…”

Section: Research Articlementioning

confidence: 99%

Design and Screening of Gallic Acid Derivatives as Inhibitors of Malarial Dihydrofolate Reductase (Dhfr) by in Silico Docking

Arsianti

Astuty

Fadilah

et al. 2017

Asian J Pharm Clin Res

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Objective: Malaria is an infection disease caused by Plasmodium parasite with high prevalence in tropic and subtropic countries. The aim of this work was to design and screening of gallic acid derivatives as inhibitors of malarial dihydrofolate reductase (DHFR) by in silico docking. Methods:The derivatives were designed by expanding the carboxyl group of gallic acid with open-chain moiety of L-threonine-allyl esters, as well as to modify the hydroxyl groups on the aromatic ring of gallic acid with methoxyl group in the derivatives. In silico approach has been utilized in finding the potential antimalaria of gallic acid derivatives. Fourteen gallic acid derivatives (compound 2-15) were modeled into three-dimensional (3D) structures by ACD Labs software. Geometry optimization and minimization of energy 3D structure of gallic acid derivatives as ligands using the MOE software. Docking process and amino acid analysis were executed using MOE software. Results:In silico docking study resulted in the three top-ranked compounds, namely, compound 5, 8, and 12. Among those three top-ranked compounds, compound 12 (octyl gallate) exhibited the strongest interaction and greatest inhibitory activity against the receptor of malarial DHFR. ConclusionOur results clearly demonstrated that compound 12 (octyl gallate) could be developed as a promising candidate for the new antimalarial agent.

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Section: Research Articlementioning

confidence: 99%

Design and Screening of Gallic Acid Derivatives as Inhibitors of Malarial Dihydrofolate Reductase (Dhfr) by in Silico Docking

Arsianti

Astuty

Fadilah

et al. 2017

Asian J Pharm Clin Res

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“…The cancer treatment by surgery, radiation, chemotherapy and cancer drug usage has not shown satisfactory result yet so that the research and development of the drug for the cancer treatment is still very needed. The development of modern computational chemistry and computational biology plays a vital role in drug discovery process for diseases causing proteins such as cancer (Ravi et al, 2012;Arsianti et al, 2014). Today, the modern computational chemistry by molecular docking methods are widely used in the early stages of drug discovery, purposing to rank potential inhibitors as an alternative to the experiments in the laboratory.…”

Section: Introductionmentioning

confidence: 99%

Molecular Docking of Citronellol, Geraniol and Ester Derivatives as Pim 1 Kinase Inhibitor of Leukemia Cancer

Widiyarti

Firdayani²,

Hanafi

et al. 2019

Valensi

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The proviral insertion site in Moloney murine leukemia virus-1 (Pim1) kinase is overexpressed in many human cancer diseases. Inhibition of Pim1 kinase has been reported can suppress cell proliferation and induce apoptotic cell death, so that the protein could be chosen as drug target for the treatment of cancer. Citronellol and geraniol mainly contained in citronella oil that's one of Indonesian natural products have bioactivity as antitumor agents, so that both of the compounds can be used as guiding compound to be developed as chemoprevention and chemotherapeutic agent compounds for cancer especially for leukemia cancer. In this research, sixteen citronellol and geraniol esters as an inhibitor of leukemia cancer designed were docked based on their interaction with leukemia receptor target of Pim1 kinase by using Molegro Virtual Docker (MVD). The result showed that the binding citronellol and geraniol esters to Pim1 kinase are more stable and better affinity than the binding between citronellol and geraniol, indicated by rerank score were lower than rerank score of citronellol/geraniol-Pim1 kinase. The docking resulted in the four top-ranked compounds, namely, citronellyl caproate, citronellyl caprylate, geranyl caproate and geranyl caprylate with rerank score value from -182.560 to -189.822 KJ/mol. These compounds have hydrogen bonding with amino acid residues of Lys 67 and Asp 186 of an active site of Pim1 kinase. Based on Lipinski's rule of five, among of the four top-ranked compounds, citronellyl caproate and geranyl caproate were predicted have potency as new chemopreventive and chemotherapeutic agents for leukemia anticancer candidates.

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“…In 2012, we have succeeded in synthesizing 18-membered analogue of antimycin A 3 which demonstrated a strong cytotoxicity against HeLa cells, Breast MDA-MB-231 cells and prostate PC-3 cells [ 14 ]. In 2014, we have simulated some antimycin A 3 analogues as inhibitors of anti-apoptotic Bcl-2 of breast cancer by in silico molecular docking [ 15 ]. In this work, as our continuing research to discover potential antibiotic anticancer agents, we focused on the in silico study and cytotoxicity evaluation of the synthezid open-chain analogues of antimycin A 3 against HEP-2 laryngeal cancer cells.…”

Section: Introductionmentioning

confidence: 99%

In Silico Study and Cytotoxicity of the Synthesized Open-chain Analogues of Antimycin A3 Against HEP-2 Laryngeal Cancer Cells

Arsianti

Fadilah

Kusmardi

et al. 2017

CCTR

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Background: Laryngeal cancers affect one quarter of all head and neck cancers. Chemotherapy is a standard method in treatment laryngeal carcinoma. How-ever, cancer chemotherapy is often a failure due to the appearance of drug resistance. This fact suggests that the search for novel, safe, and more effective laryngeal cancer drugs are required. Antimycin A3 is a fit ligand of anti-apoptotic Bcl-2. While Bcl-2 is known to be over-expressed in laryngeal cancer cell, it is quite reasonable to expect an-timycin A3 and its analogue to induce apoptosis in those cells.Methods: With this viewpoint, we decided to conduct research that is aimed to evaluate cytotoxic activity of the synthesized open-chain analogues of antimycin A3 against HEP-2 laryngeal cancer cells, as well as to conduct in silico study of the analogues on receptor binding target Bcl-2 of laryngeal cancer.Results and Conclusion: Open-chain analogues of antimycin A3 were successfully syn-thesized in a good yield from Boc-L-Threonine by esterification, amidation, and Sharp-less asymmetric dihydroxylation.Consistent with in silico study, the analogues exhibited a greater anticancer activity against laryngeal HEP-2 cells than the original antimycin A3 with IC50 ranging of 31.6 µM to 46.3 µM. Our results clearly demonstrate that the open-chain analogues of an-timycin A3 as a promising candidates of new anti-laryngeal cancer agents.

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Design and Molecular Docking Study of Antimycin A<sub>3</sub> Analogues as Inhibitors of Anti-Apoptotic Bcl-2 of Breast Cancer

Cited by 10 publications

References 14 publications

Design and Screening of Gallic Acid Derivatives as Inhibitors of Malarial Dihydrofolate Reductase (Dhfr) by in Silico Docking

Design and Screening of Gallic Acid Derivatives as Inhibitors of Malarial Dihydrofolate Reductase (Dhfr) by in Silico Docking

Molecular Docking of Citronellol, Geraniol and Ester Derivatives as Pim 1 Kinase Inhibitor of Leukemia Cancer

In Silico Study and Cytotoxicity of the Synthesized Open-chain Analogues of Antimycin A3 Against HEP-2 Laryngeal Cancer Cells

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