Browsing by Author "Gupta, Jeetendra Kumar"

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Alkaloid-based modulators of the PI3K/Akt/mTOR pathway for cancer therapy: Understandings from pharmacological point of view
(Scopus, 2024) Mokhfi, Fatima Zohra; Amin, Md Al; Zehravi, Mehrukh; Sweilam, Sherouk Hussein; Arjun, Uppuluri Varuna Naga Venkata; Gupta, Jeetendra Kumar; Vallamkonda, Bhaskar; Balakrishnan, Anitha; Challa, Manjula; Singh, Jyoti; Prasad, P. Dharani; Ali, Syed Salman; Ahmad, Irfan; Doukani, Koula; Emran, Talha Bin
This review aims to summarize the role of alkaloids as potential modulators of the PI3K/Akt/mTOR (PAMT) pathway in cancer therapy. The PAMT pathway plays a critical role in cell growth, survival, and metabolism, and its dysregulation contributes to cancer hallmarks. In healthy cells, this pathway is tightly controlled. However, this pathway is frequently dysregulated in cancers and becomes abnormally active. This can happen due to mutations in genes within the pathway itself or due to other factors. This chronic overactivity promotes cancer hallmarks such as uncontrolled cell division, resistance to cell death, and increased blood vessel formation to nourish the tumor. As a result, the PAMT pathway is a crucial therapeutic target for cancer. Researchers are developing drugs that specifically target different components of this pathway, aiming to turn it off and slow cancer progression. Alkaloids, a class of naturally occurring nitrogen-containing molecules found in plants, have emerged as potential therapeutic agents. These alkaloids can target different points within the PAMT pathway, inhibiting its activity and potentially resulting in cancer cell death or suppression of tumor growth. Research is ongoing to explore the role of various alkaloids in cancer treatment. Berberine reduces mTOR activity and increases apoptosis by targeting the PAMT pathway, inhibiting cancer cell proliferation. Lycorine inhibits Akt phosphorylation and mTOR activation, increasing pro-apoptotic protein production and decreasing cell viability. In glioblastoma models, harmine suppresses mTORC1. This review focuses on alkaloids such as evodiamine, hirsuteine, chaetocochin J, indole-3-carbinol, noscapine, berberine, piperlongumine, and so on, which have shown promise in targeting the PAMT pathway. Clinical studies evaluating alkaloids as part of cancer treatment are underway, and their potential impact on patient outcomes is being investigated. In summary, alkaloids represent a promising avenue for targeting the dysregulated PAMT pathway in cancer, and further research is warranted.
Alkaloid-based Modulators of the PI3K/AKT/MTOR Pathway for Cancer Therapy: Understandings from Pharmacological Point of View
(Elsevier, 2024-10-01) Mokhfi, Fatima Zohra; Amin, Md Al; Zehravi, Mehrukh; Sweilam, Sherouk Hussein; Arjun, Uppuluri Varuna Naga Venkata; Gupta, Jeetendra Kumar; Vallamkonda, Bhaskar; Balakrishnan, Anitha; Challa, Manjula; Singh, Jyoti; Prasad, Dharani; Ali, Syed Salman; Ahmad, Irfan; Doukani, Koula; Emran, Talha Bin
This review aims to summarize the role of alkaloids as potential modulators of the PI3K/Akt/mTOR (PAMT) pathway in cancer therapy. The PAMT pathway plays a critical role in cell growth, survival, and metabolism, and its dysregulation contributes to cancer hallmarks. In healthy cells, this pathway is tightly controlled. However, this pathway is frequently dysregulated in cancers and becomes abnormally active. This can happen due to mutations in genes within the pathway itself or due to other factors. This chronic overactivity promotes cancer hallmarks such as uncontrolled cell division, resistance to cell death, and increased blood vessel formation to nourish the tumor. As a result, the PAMT pathway is a crucial therapeutic target for cancer. Researchers are developing drugs that specifically target different components of this pathway, aiming to turn it off and slow cancer progression. Alkaloids, a class of naturally occurring nitrogen-containing molecules found in plants, have emerged as potential therapeutic agents. These alkaloids can target different points within the PAMT pathway, inhibiting its activity and potentially resulting in cancer cell death or suppression of tumor growth. Research is ongoing to explore the role of various alkaloids in cancer treatment. Berberine reduces mTOR activity and increases apoptosis by targeting the PAMT pathway, inhibiting cancer cell proliferation. Lycorine inhibits Akt phosphorylation and mTOR activation, increasing pro-apoptotic protein production and decreasing cell viability. In glioblastoma models, harmine suppresses mTORC1. This review focuses on alkaloids such as evodiamine, hirsuteine, chaetocochin J, indole-3-carbinol, noscapine, berberine, piperlongumine, and so on, which have shown promise in targeting the PAMT pathway. Clinical studies evaluating alkaloids as part of cancer treatment are underway, and their potential impact on patient outcomes is being investigated. In summary, alkaloids represent a promising avenue for targeting the dysregulated PAMT pathway in cancer, and further research is warranted.
Bioactive Molecules From Terrestrial and Seafood Resources in Hypertension Treatment
(Springer Nature Limited, 2023-10-30) Islam, Md. Rezaul; Dhar, Puja Sutro; Akash, Shopnil; Syed, Sabeena Hussain; Gupta, Jeetendra Kumar; Gandla, Kumaraswamy; Akter, Muniya; Rauf, Abdur; Hemeg, Hassan A.; Anwar, Yasir; Aljohny, Bassam Oudh; Wilairatana, Polrat
Hypertension (HTN), a complex cardiovascular disease (CVD), significantly impacts global health, prompting a growing interest in complementary and alternative therapeutic approaches. This review article seeks to provide an up-to-date and thorough summary of modern therapeutic techniques for treating HTN, with an emphasis on the molecular mechanisms of action found in substances found in plants, herbs, and seafood. Bioactive molecules have been a significant source of novel therapeutics and are crucial in developing and testing new HTN remedies. Recent advances in science have made it possible to understand the complex molecular mechanisms underlying blood pressure (BP)-regulating effects of these natural substances better. Polyphenols, flavonoids, alkaloids, and peptides are examples of bioactive compounds that have demonstrated promise in influencing several pathways involved in regulating vascular tone, reducing oxidative stress (OS), reducing inflammation, and improving endothelial function. The article explains the vasodilatory, diuretic, and renin–angiotensin–aldosterone system (RAAS) modifying properties of vital plants such as garlic and olive leaf. Phytochemicals from plants are the primary in traditional drug development as models for novel antihypertensive drugs, providing diverse strategies to combat HTN due to their biological actions. The review also discusses the functions of calcium channel blockers originating from natural sources, angiotensin-converting enzyme (ACE) inhibitors, and nitric oxide (NO) donors. Including seafood components in this study demonstrates the increased interest in using bioactive chemicals originating from marine sources to treat HTN. Omega-3 fatty acids, peptides, and minerals obtained from seafood sources have anti-inflammatory, vasodilatory, and antioxidant properties that improve vascular health and control BP. Overall, we discussed the multiple functions of bioactive molecules and seafood components in the treatment of HTN.
Identifying Potent Breast Cancer Inhibitors Against ERα Target Using Pharmacophore Model, 3D-QSAR and MD Studies
(Scopus, 2024) Rajagopal, Kalirajan; Arumugasamy, Pandiselvi; Raman, Kannan; Jupudi, Srikanth; Byran, Gowramma; Gupta, Jeetendra Kumar; Prema, S.; Kankate, Rani S.; Elansari, Lamyae; Hossain, Nazmul
the current investigation, 109 known ERα inhibitors have been developed in the current research; pharmacophore modeling, Molecular docking, MM-GBSA, and MD study have been performed to investigate the binding affinity of 9-anilinoacridines with heterocyclic substitutes as selective ERα inhibitors for breast carcinoma. Pharmacophore model have been developed by Schrodinger suite 2019–2 phasemodule. To predict binding free energy of the ligands in complex with PDB and post docked energy minimization was performed by Prime, MM-GB/SA module. The Induced fit docking studies were performed on the ligand modulated dynamic behaviour of the protein molecular dynamics study. A statistical substantial 3D - QSAR design was created using the pharmacophore hypothesis. 109 known ERα inhibitors have been developed with pIC50 values between 4.0 and 6.0 and were used in ligand-based pharmacophore modelling and 3D-QSAR analysis. R2 (0.8294), Q2 (0.7~0.8), and F value (83.5) were used to statistically validate the developed five-point hypothesis DHRRR1 employing a minimum square of four. Molecular dynamics simulations were run to comprehend the conformational changes and ligand stability at the protein active pocket. The predicted 3D-QSAR model significantly correlated with experimentally reported in-vitro antitumor activity. These in-silico discoveries will help in the future search for potent ERα inhibitors with desirable pharmacophoric properties.
Identifying Potent Breast Cancer Inhibitors Against ERα Target Using Pharmacophore Model, 3D-QSAR and MD Studies
(John Wiley & Sons, 2024-08-24) Rajagopal, Kalirajan; Arumugasamy, Pandiselvi; Raman, Kannan; Jupudi, Srikanth; Byran, Gowramma; Gupta, Jeetendra Kumar; Kankate, Prema, Rani S.; Elansari, Lamyae; Hossain, Nazmul
The current investigation, 109 known ERα inhibitors have been developed in the current research; pharmacophore modeling, Molecular docking, MM-GBSA, and MD study have been performed to investigate the binding affinity of 9-anilinoacridines with heterocyclic substitutes as selective ERα inhibitors for breast carcinoma. Pharmacophore model have been developed by Schrodinger suite 2019–2 phasemodule. To predict binding free energy of the ligands in complex with PDB and post docked energy minimization was performed by Prime, MM-GB/SA module. The Induced fit docking studies were performed on the ligand modulated dynamic behaviour of the protein molecular dynamics study. A statistical substantial 3D - QSAR design was created using the pharmacophore hypothesis. 109 known ERα inhibitors have been developed with pIC50 values between 4.0 and 6.0 and were used in ligand-based pharmacophore modelling and 3D-QSAR analysis. R2 (0.8294), Q2 (0.7~0.8), and F value (83.5) were used to statistically validate the developed five-point hypothesis DHRRR1 employing a minimum square of four. Molecular dynamics simulations were run to comprehend the conformational changes and ligand stability at the protein active pocket. The predicted 3D-QSAR model significantly correlated with experimentally reported in-vitro antitumor activity. These in-silico discoveries will help in the future search for potent ERα inhibitors with desirable pharmacophoric properties.
Recent Perspective on the Potential Role of Phytocompounds in the Prevention of Gastric Cancer
(Elsevier, 2023-12-15) Islam, Md. Rezaul; Rauf, Abdur; Akash, Shopnil; Kumer, Ajoy; Hussain, Md Sadique; Akter, Smrity; Gupta, Jeetendra Kumar; Ansari, L.H. Thameemul; Raj, Mir Md. Mahfoj Islam; Emran, Talha Bin; Aljohani, Abdullah S.M.; Abdulmonem, Waleed Al; Thiruvengadam, Rekha; Thiruvengadam, Muthu
Gastric cancer (GC) is a serious global health concern. GC is a form of cancer that advances through the stomach lining. Therefore, there is a requirement to explore novel preventive strategies for GC. A novel study indicated that plant-derived compounds have significant anticancer properties and may provide a novel therapeutic approach for GC. Recent research has highlighted the potential role of natural compounds, particularly phytocompounds, in preventing GC. Compounds, such as curcumin, resveratrol, and epigallocatechin gallate, have significant anticancer properties against GC. The primary purpose of this study was to investigate the preventive properties of the phytocompounds against GC. The experimental findings included both in vitro and in vivo studies, clinical trials, and epidemiological investigations, providing a comprehensive evaluation of the potential impact of compounds on GC prevention. This review also provides a detailed overview of the probable medicinal effects of phytocompounds on the avoidance and treatment of GC, considering their complex molecular mechanisms of action, bioavailability, and safety. This study provides new perspectives on the possible significance of compounds in GC treatment and emphasizes their promise as a cutting-edge approach.
Research Progress of Indole Alkaloids: Targeting MAP Kinase Signaling Pathways in Cancer Treatment
(MDPI Publications, 2023-11-07) Al Amin, Md.; Emran, Talha Bin; Khan, Jishan; Zehravi, Mehrukh; Sharma, Indu; Patil, Anasuya; Gupta, Jeetendra Kumar; Jeslin, D.; Krishnan, Karthickeyan; Das, Rajib; Nainu, Firzan; Ahmad, Irfan; Wilairatana, Polrat
Cancer is the leading cause of morbidity and mortality in people throughout the world. There are many signaling pathways associated with cancerous diseases, from which the Mitogen-activated protein kinase (MAPK) pathway performs a significant role in this regard. Apoptosis and proliferation are correlated with MAPK signaling pathways. Plenty of experimental investigations were carried out to assess the role of indole alkaloids in MAPK-mediated cancerous diseases. Previous reports established that indole alkaloids, such as vincristine and evodiamine are useful small molecules in cancer treatment via the MAPK signaling system. Indole alkaloids have the anticancer potential through different pathways. Vincristine and evodiamine are naturally occurring indole alkaloids that have strong anticancer properties. Additionally, much research is ongoing or completed with molecules belonging to this group. The current review aims to evaluate how indole alkaloids affect the MAPK signaling pathway in cancer treatment. Additionally, we focused on the advancement in the role of indole alkaloids, with the intention of modifying the MAPK signaling pathways to investigate potential new anticancer small molecules. Furthermore, clinical trials with indole alkaloids in cancer treatment are also highlighted.
Resveratrol: A Natural Compound Targeting the PI3K/Akt/mTOR Pathway in Neurological Diseases
(Springer Nature, 2024-11-23) Biswajit Kumar Utpal, Biswajit Kumar; Mokhfi, Fatima Zohra; Zehravi, Mehrukh; Sweilam, Sherouk Hussein; Gupta, Jeetendra Kumar; Kareemulla, Shaik; Darwin, Ronald; Rao, A. Anka; Kumar, Voleti Vijaya; Pavankumar Krosuri, Pavankumar; Prasad, Dharani; Khan, Sharukh L.; Roy, Sajib Chandra; Rab, Safia Obaidur; Alshehri, Mohammed Ali; Emran, Talha Bin
Neurological diseases (NDs), including neurodegenerative disorders and acute injuries, are a significant global health concern. The PI3K/Akt/mTOR pathway, a crucial signaling cascade, is responsible for the survival of cells, proliferation, and metabolism. Dysregulation of this pathway has been linked to neurological conditions, indicating its potential as a vital target for therapeutic approaches. Resveratrol (RSV), a natural compound found in berries, peanuts, and red grapes, has antioxidant, anti-cancer, and anti-inflammatory effects. Its ability to modulate the PI3K/Akt/mTOR pathway has been interesting in NDs. Studies have shown that RSV can activate the PI3K/Akt pathway, promoting cell survival and inhibiting apoptosis of neuronal cells. Its impact on mTOR, a downstream effector of Akt, further contributes to its neuroprotective effects. RSV’s ability to restore autophagic flux presents a promising avenue for therapeutic intervention. Its anti-inflammatory properties suppress inflammatory responses by inhibiting key signaling molecules within the pathway. Additionally, RSV’s role in enhancing mitochondrial function contributes to its neuroprotective profile. This study highlights RSV’s potential as a multifaceted therapeutic agent in NDs, specifically by PI3K/Akt/mTOR pathway modulation. Additional investigation is required to optimize its therapeutic capacity in diverse neurological conditions.