• Asian Pacific Journal of Cancer Prevention
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• 제16권18호
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• pp.8191-8196
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• 2016

Inhibition of EGFR-EGF interactions forms an important therapeutic rationale in treatment of non-small cell lung carcinoma. Established inhibitors have been successful in reducing proliferative processes observed in NSCLC, however patients suffer serious side effects. Considering the narrow therapeutic window of present EGFR inhibitors, the present study centred on identifying high efficacy EGFR inhibitors through structure based virtual screening strategies. Established inhibitors - Afatinib, Dacomitinib, Erlotinib, Lapatinib, Rociletinib formed parent compounds to retrieve similar compounds by linear fingerprint based tanimoto search with a threshold of 90%. The compounds (parents and respective similars) were docked at the EGF binding cleft of EGFR. Patch dock supervised protein-protein interactions were established between EGF and ligand (query and similar) bound and free states of EGFR. Compounds ADS103317, AKOS024836912, AGN-PC-0MXVWT, GNF-Pf-3539, SCHEMBL15205939 were retrieved respectively similar to Afatinib, Dacomitinib, Erlotinib, Lapatinib, Rociletinib. Compound-AGN-PC-0MXVWT akin to Erlotinib showed highest affinity against EGFR amongst all the compounds (parent and similar) assessed in the study. Further, AGN-PC-0MXVWT brought about significant blocking of EGFR-EGF interactions in addition showed appreciable ADMET properties and pharmacophoric features. In the study, we report AGN-PC-0MXVWT to be an efficient and high efficacy inhibitor of EGFR-EGF interactions identified through computational approaches.

• Asian Pacific Journal of Cancer Prevention
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• 제16권9호
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• pp.3759-3765
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• 2015

Background: Approaches in disruption of MDM2-p53 interactions have now emerged as an important therapeutic strategy in resurrecting wild type p53 functional status. The present study highlights virtual screening strategies in identification of high affinity small molecule non-peptidic inhibitors. Nutlin3A and RG7112 belonging to compound class of Cis-imidazoline, MI219 of Spiro-oxindole class and Benzodiazepine derived TDP 665759 served as query small molecules for similarity search with a threshold of 95%. The query molecules and the similar molecules corresponding to each query were docked at the transactivation binding cleft of MDM2 protein. Aided by MolDock algorithm, high affinity compound against MDM2 was retrieved. Patch Dock supervised Protein-Protein interactions were established between MDM2 and ligand (query and similar) bound and free states of p53. Compounds with PubCid 68870345, 77819398, 71132874, and 11952782 respectively structurally similar to Nutlin3A, RG7112, Mi219 and TDP 665759 demonstrated higher affinity to MDM2 in comparison to their parent compounds. Evident from the protein-protein interaction studies, all the similar compounds except for 77819398 (similar to RG 7112) showed appreciable inhibitory potential. Of particular relevance, compound 68870345 akin to Nutlin 3A had highest inhibitory potential that respectively showed 1.3, 1.2, 1.16 and 1.26 folds higher inhibitory potential than Nutilin 3A, MI 219, RG 7112 and TDP 1665759. Compound 68870345 was further mapped for structure based pharamacophoric features. In the study, we report Cis-imidazoline derivative compound; Pubcid: 68870345 to have highest inhibitory potential in blocking MDM2-p53 interactions hitherto discovered.

• Fisheries and Aquatic Sciences
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• 제25권2호
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• pp.49-63
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• 2022

Anti-cholinesterase (ChE)s are commonly prescribed as the symptomatic treatment of Alzheimer's disease. They are applied to prevent the breakdown of neurotransmitter acetylcholine (ACh) that bind to muscarinic and nicotinic receptors in the synaptic cleft. Seaweeds are one of the richest sources of bioactive compounds for both nutraceuticals and pharmacognosy applications. This study aimed to determine the anti-ChEs activity of Gracilaria manilaensis, one of the red seaweeds notables for its economic importance as food and raw materials for agar production. Methanol extracts (GMM) of G. manilaensis were prepared through maceration, and further purified with column chromatography into a semi-pure fraction. Ellman assay was carried out to determine the anti-acetylcholinesterase (AChE) and anti-butyrylcholinesterase (BuChE) activities of extracts and fractions. Lineweaver-Burk plot analysis was carried out to determine the inhibition kinetic of potent extract and fraction. Major compound(s) from the most potent fraction was determined by liquid chromatography-mass spectrometry (LCMS). GMM and fraction G (GMMG) showed significant inhibitory activity AChE with EC₅₀ of 2.6 mg/mL and 2.3 mg/mL respectively. GMM and GMMG exhibit mixed-inhibition and uncompetitive inhibition respectively against AChE. GMMG possesses neuroprotective compounds such as cynerine A, graveolinine, militarinone A, eplerenone and curumenol. These findings showed a promising insight of G. manilaensis to be served as a nutraceutical for neuronal health care in the future.

• 식물분류학회지
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• 제36권3호
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• pp.163-187
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• 2006

태백제비꽃파 근연 분류군인 단풍제비꽃과 남산제비꽃의 종간 유연관계를 알아보기 위하여 극단적인 형태를 보이는 7개 집단에 대해 외부형태학적, 화분학적, 해부학적 형질에 대한 분류학적 연구와, 국내에 분포하는 분류군을 비롯하여 유럽, 중국과 일본에 분포하는 근연 분류군을 포함한 28개 집단에 대한 핵 DNA의 ITS와 V. pinnata를 제외한 27집단에 대한 엽록체 DNA의 trnL-F 지역에 대한 분자계통학적 연구를 수행하였다. 외부형태학적 형질에서 엽연 거치의 수, 화피의 크기, 주두와 종자의 형질 등은 형태가 유사하거나 중복되는 형질을 갖는 것으로 나타나 구분이 불가능 하였으나 잎의 모양에 의해서는 두 그룹으로 유집되었다. 화분은 단립으로 극면입상은 반각형이었고, 발아구는 3공구형이며, 표면의 돌기는 미립상, 표면무늬는 난선상으로 집단간 유사한 특징을 보였다. 화분입상은 5개 집단이 장구형으로 관찰된 반면 단풍제비꽃 type 1과 남산제비꽃 type 3은 아장구형으로 나타났다. 해부학적 형질에서 엽병, 화경, 뿌리와 주맥의 횡단면을 관찰한 결과는 7개 집단이 유사한 형태로 나타나 차이점을 찾을 수 없었으며, 기공은 모두 잎의 아랫면에만 존재하였고, 단위 면적당 기공의 수는 결각이 심할수록 많은 것으로 나타났다. 핵 DNA의 ITS지역에 대한 염기서열 분석 결과 V. pinnata와 V. dissecta는 단계통을 형성하였고 군외군으로 부터 가장 먼저 분지되어 독립된 분계조를 형성하면서 나머지 분류군들을 위한 자매군으로 유집되어 태백제비꽃과 근연 분류군을 위한 조상형으로의 가능성을 제시하였다. 그러나 태백제비꽃의 종내분류군과 V. eizanensis가 포함된 그룹은 뚜렷한 분계조를 형성하지 않았다. 이러한 결과는 엽록체 DNA의 trnL-F 지역에 대한 결과에서도 유사한 경향올 보였다. 이상의 결과에서 잎의 모양을 제외한 나머지 형질들은 태백제비꽃과 근연 분류군들을 구별하는데 유용하지 않은 것으로 확인되어 단풍제비꽃과 남산제비꽃은 태백제비꽃의 종하 분류군으로 취급하는 것이 타당할 것으로 판단된다.