Molecular docking of two cytotoxic compounds from Calotropis gigantea leaves against therapeutic molecular target of pancreatic cancer
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ABSTRACT:
SUBMITTER: Purnama A
PROVIDER: S-EPMC10914070 | biostudies-literature | 2021 Aug
REPOSITORIES: biostudies-literature
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Project description:Calotropis gigantea is often found in mining areas with heavy metal pollution. However, little is known about the physiological and molecular response mechanism of C. gigantea to Cd stress. In the present study, Cd tolerance characteristic of C. gigantea and the potential mechanisms were explored. Seed germination test results showed that C. gigantea had a certain Cd tolerance capacity. Biochemical and transcriptomic analysis indicated that the roots and leaves of C. gigantea had different responses to early Cd stress. A total of 176 and 1618 DEGs were identified in the roots and leaves of C. gigantea treated with Cd compared to the control samples, respectively. Results indicated that oxidative stress was mainly initiated in the roots of C. gigantea, whereas the leaves activated several Cd detoxification processes to cope with Cd, including the upregulation of genes involved in Cd transport (i.e., absorption, efflux, or compartmentalization), cell wall remodeling, antioxidant system, and chelation. This study provides preliminary information to understand how C. gigantea respond to Cd stress, which is useful for evaluating the potential of C. gigantea in the remediation of Cd-contaminated soils.
| S-EPMC8955323 | biostudies-literature
Project description:Cardenolides, a group of cardiac glycosides are potent inhibitors of Na+/K+ ATPase pump in mammals, animals including insects. Some insects can circumvent the toxicity of cardenolides by mechanisms like target site resistance and metabolic resistance resulting in enhanced tolerance or adaptation. In this paper, we report an intriguing observation of a polyphagous feeder feeding gregariously on the leaves of Calotropis gigantea (L.) without any apparent adverse effect. No choice feeding assay showed higher larval biomass and reduced number of days to develop on C. gigantea leaves compared to Ricinus and banana. We found the activity of GST higher in C. gigantea fed larva and HR LC-MS analysis of Olepa sps. revealed the presence of glutathione-strophanthidin conjugate in larval body tissue. In silico molecular simulation results confirmed strong interaction between delta variant GST and glutathione-strophanthidin complex. The sequestration site and cost benefit of glutathione-strophanthidin sequestration in body tissues of Olepa sps. needs further investigation. Olepa; Calotropis gigantea; Sequester; GST; Glutathione-strophanthidin conjugate; Strophanthidin; Detoxification.
| S-EPMC9513775 | biostudies-literature
Project description:Genome and Transcriptome Sequencing of Calotropis gigantea
| PRJNA400797 | ENA
Project description:Phytochemical investigations of the ethanolic extract of leaves of Clutia lanceolata (Family: Euphorbiaceae) resulted in the isolation of four compounds viz. 3,4-dihydroxy-2-methylbenzoic acid (1), 2,2'-dihydroxy-1,1'-binaphthyl (2), 1,3,8-trihydroxy-6-methylanthracene-9,10-dione (3) and 5-hydroxy-1,7-bis(4-hydroxy-3-methoxyphenyl)hepta-1,4,6-trien-3-one (4). Although all the isolated compounds were known but this was the first report from this plant source. Their structures were established on the basis of chemical and physical evidences viz. elemental analysis, FT-IR, 1H-NMR, 13C-NMR and mass spectral analysis. Structure of compound 2 and 4 was further authenticated by single-crystal X-ray analysis and density functional theory calculations. The isolated compounds (1-4) were screened for AChE enzyme inhibition assay in which compound 3 and 4 were found to be more potent AChE inhibitor. Molecular docking study of potent AChE inhibitor was performed to find the probable binding mode of the compounds into the active site of receptor. Moreover, the isolated compounds were also screened for in vivo cytotoxicity by brine shrimp lethality assay.
| S-EPMC5136371 | biostudies-literature
Project description:Background and purposeOxadiazole-derived compounds have been shown to have a wide range of pharmacological activities. 2, 5-Disubstituted 1, 3, 4-oxadiazole derivatives have occupied a specific place in the design of anti-proliferative agents. In the present work a series of 2, 5-disubstituted 1, 3, 4-oxadiazoles derivatives containing amide group has been synthesized via a two-step reaction.Experimental approachA mixture of substituted carboxylic acid derivatives, semicarbazide, and phosphorus oxychloride in reflux condition yielded 2-amino-5-aryl-1, 3, 4-oxadiazole derivatives. Acylation of the amino group of the resultant oxadiazole with 6-chloronicotinoyl chloride in dry tetrahydrofuran/pyridine afforded the final products. The synthesized molecules were docked in the active sites of the epidermal growth factor receptor tyrosine kinase domain (PDB: 1M17) crystal structure to study the possible interactions with the active site. Cytotoxic activities of final products against HeLa and MCF-7 cells were also assessed by MTT assay.Findings/resultsCompounds IIb, IIc, and IIe had a considerable cytotoxic activity with IC50 values of 19.9, 35, and 25.1 μM, respectively against HeLa cells. The highest docking score was -7.89 kcal/mol for compound IIe.Conclusion and implicationsCompound IIe exhibited remarkable cytotoxic activity against the two tested cell lines particularly HeLa cells which was in accordance with the in silico ΔG bind result but further evaluations are necessary to prove these findings.
| S-EPMC7879786 | biostudies-literature
Project description:Two stereoisomeric cardenolides, uscharin (1) and a new compound, 2'-epi-uscharin (2), were isolated from the latex of Calotropis gigantea (Asclepiadaceae). Their structures were fully elucidated based on their spectroscopic data, X-ray crystallographic data and chemical evidences. Both epimers (1 and 2) exhibited strong inhibitory effects on HIF-1 activity with different magnitudes. Compound 1 showed much more potent activity than 2 and digoxin, a well-known HIF-1 inhibitor. Discrepancy in potencies between 1 and 2 revealed the contribution of a β-configuration of 2' hydroxyl moiety for HIF-1 inhibitory activity. This is a first report of the activity of HIF-1 inhibition of thiazoline ring-containing cardenolides.
| S-EPMC5381191 | biostudies-literature
Project description:BackgroundThe Sodom apple (Calotropis gigantea), a member of the Asclepiadaceae family, is a large evergreen shrub native to continental Asia and northern Africa. As an important medicinal shrub and a fiber resource plant, there is an urgent need for developing molecular markers to facilitate breeding and genetic improvement of varieties.ResultsIn this study, using the Illumina high throughput sequencing technique we obtained about 45 million paired end sequencing reads, De novo assembled and generated a total of 133,634 transcripts with a mean of 1837.47 bp in length. Based on protein homology searches against available databases, a total of 21,851 unigenes were functionally annotated. In particular, many transcripts that encode for putative proteins involved in fiber and secondary metabolite biosynthesis were identified and analyzed. Key fiber genes identified were validated experimentally through Real-Time PCR technique. Various transcription factors involved in regulating plant response to abiotic stress were also identified. In addition, based on the unigene sequences assembled, 11,623 microsatellites loci were detected, which provide very useful resources for developing microsatellite molecular markers.ConclusionThis study is the first report on transcriptome information in the Calotropis species and provides rich gene transcript resources for conducting further studies on understanding the molecular basis of fiber and secondary metabolite biosynthesis, serving the genetic improvement and resource utilization in Calotropis plants.
| S-EPMC4580217 | biostudies-literature