Publications by authors named "Khaled Mahmud Sujon"

3 Publications

  • Page 1 of 1

Unfolding the apoptotic mechanism of antioxidant enriched-leaves of Tabebuia pallida (lindl.) miers in EAC cells and mouse model.

J Ethnopharmacol 2021 Oct 10;278:114297. Epub 2021 Jun 10.

Department of Pharmacy, University of Rajshahi, Rajshahi, 6205, Bangladesh. Electronic address:

Ethnopharmacological Relevance: Tabebuia pallida (Lindl.) Miers (T. pallida) is a well-known native Caribbean medicinal plant. The leaves and barks of T. pallida are used as traditional medicine in the form of herbal or medicinal tea to manage cancer, fever, and pain. Moreover, extracts from the leaves of T. pallida showed anticancer activity. However, the chemical profile and mechanism of anticancer activity of T. pallida leaves (TPL), stem bark (TPSB), root bark (TPRB) and flowers (TPF) remain unexplored.

Aim Of The Study: The present study was designed to explore the regulation of apoptosis by T. pallida using Ehrlich Ascites Carcinoma (EAC) cultured cells and an EAC mouse model. LC-ESI-MS/MS was used for compositional analysis of T. pallida extracts.

Materials And Methods: Dried and powdered TPL, TPSB, TPRB and TPF were extracted with 80% methanol. Using cultured EAC cells and EAC-bearing mice with and without these extracts, anticancer activities were studied by assessing cytotoxicity and tumor cell growth inhibition, changes in life span of mice, and hematological and biochemical parameters. Apoptosis was analyzed by microscopy and expression of selected apoptosis-related genes (Bcl-2, Bcl-xL, NFκ-B, PARP-1, p53, Bax, caspase-3 and -8) using RT-PCR. LC-ESI-MS analysis was performed to identify the major compounds from active extracts. Computer aided analyses was undertaken to sort out the best-fit phytoconstituent of total ten isolated compounds of this plant for antioxidant and anticancer activity.

Results: In EAC mice compared with untreated controls, the TPL extract exhibited the highest cancer cell toxicity with significant tumor cell growth inhibition (p < 0.001), reduced ascites by body weight (p < 0.01), increased the life span (p < 0.001), normalized blood parameters (RBC/WBC counts), and increased the levels of superoxide dismutase and catalase. TPL-treated EAC cells showed increased apoptotic characteristics of membrane blebbing, chromatin condensation and nuclear fragmentation, and caspase-3 activation, compared with untreated EAC cells. Moreover, annexin V-FITC and propidium iodide signals were greatly enhanced in response to TPL treatment, indicating apoptosis induction. Pro- and anti-apoptotic signaling after TPL treatment demonstrated up-regulated p53, Bax and PARP-1, and down-regulated NFκ-B, Bcl-2 and Bcl-xL expression, suggesting that TPL shifts the balance of pro- and anti-apoptotic genes towards cell death. LC-ESI-MS data of TPL showed a mixture of glycosides, lapachol, and quercetin antioxidant and its derivatives that were significantly linked to cancer cell targets. The compound, pelargonidin-3-O-glucoside was found to be most effective in computer aided models.

Conclusions: In conclusion, the TPL extract of T. pallida possesses significant anticancer activity. The tumor suppressive mechanism is due to apoptosis induced by activation of antioxidant enzymes and caspases and mediated by a change in the balance of pro- and anti-apoptotic genes that promotes cell death.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1016/j.jep.2021.114297DOI Listing
October 2021

Molecular docking and dynamics study of natural compound for potential inhibition of main protease of SARS-CoV-2.

J Biomol Struct Dyn 2021 Oct 24;39(16):6281-6289. Epub 2020 Jul 24.

Department of Genetic Engineering and Biotechnology, University of Rajshahi, Rajshahi, Bangladesh.

Newly emerged SARS-CoV-2 made recent pandemic situations across the globe is accountable for countless unwanted death and insufferable panic associated with co-morbidities among mass people. The scarcity of appropriate medical treatment and no effective vaccine or medicine against SARS-CoV-2 has turned the situation worst. Therefore, in this study, we made a deep literature review to enlist plant-derived natural compounds and considered their binding mechanism with the main protease of SARS-CoV-2 through combinatorial bioinformatics approaches. Among all, a total of 14 compounds were filtered where Carinol, Albanin, Myricetin were had better binding profile than the rest of the compounds with having binding energy of -8.476, -8.036, -8.439 kcal/mol, respectively. Furthermore, MM-GBSA calculations were also considered in this selection process to support docking studies. Besides, 100 ns molecular dynamics simulation endorsed the rigid nature, less conformational variation and binding stiffness. As this study, represents a perfect model for SARS-CoV-2 main protease inhibition through bioinformatics study, these potential drug candidates may assist the researchers to find a superior and effective solution against COVID-19 after future experiments.Communicated by Ramaswamy Sarma.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1080/07391102.2020.1796808DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7441771PMC
October 2021

Exploring the potent inhibitors and binding modes of phospholipase A2 through in silico investigation.

J Biomol Struct Dyn 2020 Sep 23;38(14):4221-4231. Epub 2019 Oct 23.

Department of Biochemistry and Biotechnology, University of Science and Technology Chittagong (USTC), Chittagong, Bangladesh.

Snake venom of comprises of several types of enzymes, and among them, water-soluble proteolytic enzyme, phospholipase A2 (PLA), is noteworthy for its numerous adverse effects, such as cytotoxicity, cardiotoxicity, hemolytic, anti-coagulant, and hypotensive effects, including being highly potent as a neurotoxin. Limited anti-venom therapy (with their lower efficacy) has attracted considerable pharmacological interest to develop potent inhibitors of PLA. Thus, 34 experimentally proven and diverse synthetic inhibitors of PLA were screened primarily on the basis of Glide extra precision docking and MM-GBSA rescoring function. Then, ten potential hits were subjected to induced fit docking, in which top three potential inhibitors were considered, and those were found to interact with Ca, disulfide binding site, and phosphatidylcholine activation sites, thereby, possibly disrupting the catalytic activity of Ca as well as the inflammatory functions of PLA. These compounds showed positive remarks on various physiochemical properties and pharmacologically relevant descriptors. Gap energy and thermodynamic properties were investigated by employing density functional theory for all compounds to understand their chemical reactivity and thermodynamic stability. Molecular dynamics simulation was performed for 100 ns in order to evaluate the stability and binding modes of docked complexes, and the energy of binding was calculated through MM-PBSA analysis. On the whole, the proposed compounds could be used for targeted inhibition. Communicated by Ramaswamy H. Sarma.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1080/07391102.2019.1680440DOI Listing
September 2020
-->