Resistance towards chemotherapy and radiotherapy as well as relapse of cancer is the major obstac... more Resistance towards chemotherapy and radiotherapy as well as relapse of cancer is the major obstacle in the treatment of cancer. The main factor behind is cancer stem cells (CSCs) which are more resistant to conventional chemotherapy, radiotherapy and are quite able to regenerate whole new tumor again if remain alive during treatment. Targeting CSCs along with actively dividing cancer cells may significantly contribute to the solution of the problem of resistance and relapse. Various approaches are implemented to eradicate CSCs which include CSC markers specific compounds, Drugs which disturb niche and various inhibitors/modulators of signaling pathways. Hedgehog (Hh), Wnt and Notch pathways are modulated/inhibited using various agents and shown beneficial results in multiple forms of cancer. Many inhibitors/modulators of these pathways have been entered in the clinical trials. MicroRNAs have also been developed as anti CSCs agents. In this review, we have covered current status of CSC targeting therapy based on CSC markers, CSC niche, Hedgehog, Wnt, Notch pathway along with MicroRNA based targeting strategies and possibility of implementation multi-targeted anti-CSC therapy for the better outcome of the results.
INTRODUCTION: A facile, convenient and general method has been developed for the one-pot three-co... more INTRODUCTION: A facile, convenient and general method has been developed for the one-pot three-component synthesis of structurally diverse 2-amino pyran annulated heterocycles from the reactions of aromatic aldehydes, malononitrile and various C-H activated acids in the presence of a catalytic amount of glycine as an efficient metal-free organocatalyst in aqueous ethanol under refluxed conditions. METHOD: Using this developed protocol, we were able to synthesize a series of structurally diverse 2-amino pyran derivatives viz., 2-amino-4,5-dihydropyrano[3,2-c]chromenes, 2-amino-4,5-dihydropyrano[4,3-b]pyrans, 2-amino-5,6,7,8-tetrahydro-4H-chromenes, 2'-amino-2,5'-dioxo-5'H-spiro[indoline-3,4'-pyrano[3,2-c]chromene]-3'-carbonitrile and 2'-amino-1,3,5'-trioxo-1,3-dihydro-5'H-spiro[indene-2,4'-pyrano[3,2-c]chromene]-3'-carbonitrile in excellent yields. RESULT: Synthesis of biologically promising pyrans and spiropyrans, high atom economy, excellent ...
Breast cancer is a disease where cells in the tissue of the breast, grow and divide without norma... more Breast cancer is a disease where cells in the tissue of the breast, grow and divide without normal control. Breast cancer is second major cause for death in world wide. Importance of natural product increase due to adverse effect of existing synthetic drugs. <i>Asparagus racemosus</i> comprises phytoestrogens which can be used for the treatment of breast cancer. In the current study, <i>In vitro</i> antiproliferative activity of the extracts of <i>A. racemosus</i> is performed in T47D cancer cell lines. Outcomes of the result indicated that aqueous methanol and methanol extract showed excellent antiproliferative activity as compared to bazedoxifene (standard), ethyl acetate and petroleum ether extract<i>. In silico</i> study of reported phytochemical constituents of <i>A. racemosus</i> was performed for understand the molecular mechanism and prospect pharmacophore development. Furthermore, compound <b>26</b> (ru...
Diabetes mellitus (DM) is the fastest growing metabolic disorder in the world. Recently, more att... more Diabetes mellitus (DM) is the fastest growing metabolic disorder in the world. Recently, more attention is paid to the study of natural products due to side effects of synthetic drugs. <i>Stevia rebaudiana</i> (Bertoni) is considered an encouraging starting point for the antidiabetic lead development. In the present study, the <i>in vitro</i> α-amylase inhibitory activity of the extracts of <i>S. rebaudiana</i> is investigated. In order to understand the molecular mechanism and future pharmacophore development, <i>in silico</i> study of secondary metabolites isolated from <i>S. rebaudiana</i> was carried out. Results indicated that water extract shows highest α-amylase inhibitory activity as compared to other extracts. Moreover, compound 20 (rebaudioside A) which has been previously reported and isolated from water extract showed the impressive binding profile with α-amylase. Therefore, our study suggests that <i>S. r...
Background: Cancer is the world’s third deadliest disease. Despite the availability of numerous t... more Background: Cancer is the world’s third deadliest disease. Despite the availability of numerous treatments, researchers are focusing on the development of new drugs with no resistance and toxicity issues. Many newly synthesized drugs fail to reach clinical trials due to poor pharmacokinetic properties. Therefore, there is an imperative requisite to expand novel anticancer agents with in vivo efficacy. Objective: This review emphasizes synthetic methods, contemporary strategies used for the inclusion of oxazole moiety, mechanistic targets, along with comprehensive structure-activity relationship studies to provide perspective into the rational design of highly efficient oxazole-based anticancer drugs. Methods: Literature related to oxazole derivatives engaged in cancer research is reviewed. This article gives a detailed account of synthetic strategies, targets of oxazole in cancer, including STAT3, Microtubules, G-quadruplex, DNA topoisomerases, DNA damage, protein kinases, miscellan...
Metabolites from natural sources either from terrestrial or marine sources serve as unmatched res... more Metabolites from natural sources either from terrestrial or marine sources serve as unmatched resources for new drug leads or diverse chemical identity. Due to ever-rising requirement for new pharmacophore in high-throughput screening and discovery for therapeutic drugs from metabolites, there has been motivated interest particularly in edible plants around the globe. Bioactive compounds are indispensable component present in different forms of botanicals, nutraceuticals, and herbal preparations used for the various medicinal applications. The prime focus in present chapter is to enlighten and discus diverse analytical methodologies which have been applied during extraction, isolation, and characterization of active constituents in botanicals, nutraceutical, and herbal preparations.
Breast cancer is the second most leading cause of death among women. Multiple drugs have been app... more Breast cancer is the second most leading cause of death among women. Multiple drugs have been approved by FDA for the treatment of BC. The major drawbacks of existing drugs are the development of resistance, toxicity, selectivity problem. The other therapies like hormonal therapy, surgery, radiotherapy, and immune therapy are in use but showed many side effects like bioavailability issues, non-selectivity, pharmacokinetic-pharmacodynamic problems. Therefore, there is an urgent need to develop new moieties that are nonviolent and more effective in the treatment of cancer. Isoxazole derivatives have gain popularity in recent years due to anticancer potential with the least side effects. These derivatives act as an anticancer agent with different mechanisms like inducing apoptosis, aromatase inhibition, disturbing tubulin congregation, topoisomerase inhibition, HDAC inhibition, and ERα inhibition. In this article, we have explored the synthetic strategies, anticancer mechanism of action along with SAR studies of isoxazole derivatives.
There was a golden era where everyone thought that microbes can no longer establish threat to hum... more There was a golden era where everyone thought that microbes can no longer establish threat to humans but the time has come where microbes are proposing strong resistance against the majority of antimicrobials. Over the years, the inappropriate use and easy availability of antimicrobials have made antimicrobial resistance (AMR) to emerge as the world’s third leading cause of death. Microorganisms over the time span have acquired resistance through various mechanisms such as efflux pump, transfer through plasmids causing mutation, changing antimicrobial site of action, or modifying the antimicrobial which will lead to become AMR as the main cause of death worldwide by 2030. In order to overcome the emerging resistance against majority of antimicrobials, there is a need to uncover drugs from plants because they have proved to be effective antimicrobials due to the presence of secondary metabolites such as terpenoids. Terpenoids abundant in nature are produced in response to microbial a...
Background: Breast cancer (BC) is a leading cause of cancer-related deaths in women next to skin ... more Background: Breast cancer (BC) is a leading cause of cancer-related deaths in women next to skin cancer. Estrogen receptors (ERs) play an important role in the progression of BC. Current anticancer agents have several drawbacks such as serious side effects and the emergence of resistance to chemotherapeutic drugs. As coumarins possess minimum side effect along with multi-drug reversal activity, it has a tremendous ability to regulate a diverse range of cellular pathways that can be explored for selective anticancer activity. Objectives: Synthesis and evaluation of new coumarin analogues for anti-proliferative activity on human breast cancer cell line MCF-7 along with exploration of binding interaction of the compounds for ER-α target protein by molecular docking. Method: In this study, the anti-proliferative activity of C-3 substituted coumarins analogues (1-17) has been evaluated against estrogen receptor-positive MCF-7 breast cancer cell lines. Molecular interactions and ADME stud...
Abstract Diabetes mellitus (DM) is the fastest growing metabolic disorder in the world. Recently,... more Abstract Diabetes mellitus (DM) is the fastest growing metabolic disorder in the world. Recently, more attention is paid to the study of natural products due to side effects of synthetic drugs. Stevia rebaudiana (Bertoni) is considered an encouraging starting point for the antidiabetic lead development. In the present study, the in vitro α-amylase inhibitory activity of the extracts of S. rebaudiana is investigated. In order to understand the molecular mechanism and future pharmacophore development, in silico study of secondary metabolites isolated from S. rebaudiana was carried out. Results indicated that water extract shows highest α-amylase inhibitory activity as compared to other extracts. Moreover, compound 20 (rebaudioside A) which has been previously reported and isolated from water extract showed the impressive binding profile with α-amylase. Therefore, our study suggests that S. rebaudiana could be used in the development of therapeutic drugs for the treatment of diabetes.
Resistance towards chemotherapy and radiotherapy as well as relapse of cancer is the major obstac... more Resistance towards chemotherapy and radiotherapy as well as relapse of cancer is the major obstacle in the treatment of cancer. The main factor behind is cancer stem cells (CSCs) which are more resistant to conventional chemotherapy, radiotherapy and are quite able to regenerate whole new tumor again if remain alive during treatment. Targeting CSCs along with actively dividing cancer cells may significantly contribute to the solution of the problem of resistance and relapse. Various approaches are implemented to eradicate CSCs which include CSC markers specific compounds, Drugs which disturb niche and various inhibitors/modulators of signaling pathways. Hedgehog (Hh), Wnt and Notch pathways are modulated/inhibited using various agents and shown beneficial results in multiple forms of cancer. Many inhibitors/modulators of these pathways have been entered in the clinical trials. MicroRNAs have also been developed as anti CSCs agents. In this review, we have covered current status of CSC targeting therapy based on CSC markers, CSC niche, Hedgehog, Wnt, Notch pathway along with MicroRNA based targeting strategies and possibility of implementation multi-targeted anti-CSC therapy for the better outcome of the results.
INTRODUCTION: A facile, convenient and general method has been developed for the one-pot three-co... more INTRODUCTION: A facile, convenient and general method has been developed for the one-pot three-component synthesis of structurally diverse 2-amino pyran annulated heterocycles from the reactions of aromatic aldehydes, malononitrile and various C-H activated acids in the presence of a catalytic amount of glycine as an efficient metal-free organocatalyst in aqueous ethanol under refluxed conditions. METHOD: Using this developed protocol, we were able to synthesize a series of structurally diverse 2-amino pyran derivatives viz., 2-amino-4,5-dihydropyrano[3,2-c]chromenes, 2-amino-4,5-dihydropyrano[4,3-b]pyrans, 2-amino-5,6,7,8-tetrahydro-4H-chromenes, 2'-amino-2,5'-dioxo-5'H-spiro[indoline-3,4'-pyrano[3,2-c]chromene]-3'-carbonitrile and 2'-amino-1,3,5'-trioxo-1,3-dihydro-5'H-spiro[indene-2,4'-pyrano[3,2-c]chromene]-3'-carbonitrile in excellent yields. RESULT: Synthesis of biologically promising pyrans and spiropyrans, high atom economy, excellent ...
Breast cancer is a disease where cells in the tissue of the breast, grow and divide without norma... more Breast cancer is a disease where cells in the tissue of the breast, grow and divide without normal control. Breast cancer is second major cause for death in world wide. Importance of natural product increase due to adverse effect of existing synthetic drugs. <i>Asparagus racemosus</i> comprises phytoestrogens which can be used for the treatment of breast cancer. In the current study, <i>In vitro</i> antiproliferative activity of the extracts of <i>A. racemosus</i> is performed in T47D cancer cell lines. Outcomes of the result indicated that aqueous methanol and methanol extract showed excellent antiproliferative activity as compared to bazedoxifene (standard), ethyl acetate and petroleum ether extract<i>. In silico</i> study of reported phytochemical constituents of <i>A. racemosus</i> was performed for understand the molecular mechanism and prospect pharmacophore development. Furthermore, compound <b>26</b> (ru...
Diabetes mellitus (DM) is the fastest growing metabolic disorder in the world. Recently, more att... more Diabetes mellitus (DM) is the fastest growing metabolic disorder in the world. Recently, more attention is paid to the study of natural products due to side effects of synthetic drugs. <i>Stevia rebaudiana</i> (Bertoni) is considered an encouraging starting point for the antidiabetic lead development. In the present study, the <i>in vitro</i> α-amylase inhibitory activity of the extracts of <i>S. rebaudiana</i> is investigated. In order to understand the molecular mechanism and future pharmacophore development, <i>in silico</i> study of secondary metabolites isolated from <i>S. rebaudiana</i> was carried out. Results indicated that water extract shows highest α-amylase inhibitory activity as compared to other extracts. Moreover, compound 20 (rebaudioside A) which has been previously reported and isolated from water extract showed the impressive binding profile with α-amylase. Therefore, our study suggests that <i>S. r...
Background: Cancer is the world’s third deadliest disease. Despite the availability of numerous t... more Background: Cancer is the world’s third deadliest disease. Despite the availability of numerous treatments, researchers are focusing on the development of new drugs with no resistance and toxicity issues. Many newly synthesized drugs fail to reach clinical trials due to poor pharmacokinetic properties. Therefore, there is an imperative requisite to expand novel anticancer agents with in vivo efficacy. Objective: This review emphasizes synthetic methods, contemporary strategies used for the inclusion of oxazole moiety, mechanistic targets, along with comprehensive structure-activity relationship studies to provide perspective into the rational design of highly efficient oxazole-based anticancer drugs. Methods: Literature related to oxazole derivatives engaged in cancer research is reviewed. This article gives a detailed account of synthetic strategies, targets of oxazole in cancer, including STAT3, Microtubules, G-quadruplex, DNA topoisomerases, DNA damage, protein kinases, miscellan...
Metabolites from natural sources either from terrestrial or marine sources serve as unmatched res... more Metabolites from natural sources either from terrestrial or marine sources serve as unmatched resources for new drug leads or diverse chemical identity. Due to ever-rising requirement for new pharmacophore in high-throughput screening and discovery for therapeutic drugs from metabolites, there has been motivated interest particularly in edible plants around the globe. Bioactive compounds are indispensable component present in different forms of botanicals, nutraceuticals, and herbal preparations used for the various medicinal applications. The prime focus in present chapter is to enlighten and discus diverse analytical methodologies which have been applied during extraction, isolation, and characterization of active constituents in botanicals, nutraceutical, and herbal preparations.
Breast cancer is the second most leading cause of death among women. Multiple drugs have been app... more Breast cancer is the second most leading cause of death among women. Multiple drugs have been approved by FDA for the treatment of BC. The major drawbacks of existing drugs are the development of resistance, toxicity, selectivity problem. The other therapies like hormonal therapy, surgery, radiotherapy, and immune therapy are in use but showed many side effects like bioavailability issues, non-selectivity, pharmacokinetic-pharmacodynamic problems. Therefore, there is an urgent need to develop new moieties that are nonviolent and more effective in the treatment of cancer. Isoxazole derivatives have gain popularity in recent years due to anticancer potential with the least side effects. These derivatives act as an anticancer agent with different mechanisms like inducing apoptosis, aromatase inhibition, disturbing tubulin congregation, topoisomerase inhibition, HDAC inhibition, and ERα inhibition. In this article, we have explored the synthetic strategies, anticancer mechanism of action along with SAR studies of isoxazole derivatives.
There was a golden era where everyone thought that microbes can no longer establish threat to hum... more There was a golden era where everyone thought that microbes can no longer establish threat to humans but the time has come where microbes are proposing strong resistance against the majority of antimicrobials. Over the years, the inappropriate use and easy availability of antimicrobials have made antimicrobial resistance (AMR) to emerge as the world’s third leading cause of death. Microorganisms over the time span have acquired resistance through various mechanisms such as efflux pump, transfer through plasmids causing mutation, changing antimicrobial site of action, or modifying the antimicrobial which will lead to become AMR as the main cause of death worldwide by 2030. In order to overcome the emerging resistance against majority of antimicrobials, there is a need to uncover drugs from plants because they have proved to be effective antimicrobials due to the presence of secondary metabolites such as terpenoids. Terpenoids abundant in nature are produced in response to microbial a...
Background: Breast cancer (BC) is a leading cause of cancer-related deaths in women next to skin ... more Background: Breast cancer (BC) is a leading cause of cancer-related deaths in women next to skin cancer. Estrogen receptors (ERs) play an important role in the progression of BC. Current anticancer agents have several drawbacks such as serious side effects and the emergence of resistance to chemotherapeutic drugs. As coumarins possess minimum side effect along with multi-drug reversal activity, it has a tremendous ability to regulate a diverse range of cellular pathways that can be explored for selective anticancer activity. Objectives: Synthesis and evaluation of new coumarin analogues for anti-proliferative activity on human breast cancer cell line MCF-7 along with exploration of binding interaction of the compounds for ER-α target protein by molecular docking. Method: In this study, the anti-proliferative activity of C-3 substituted coumarins analogues (1-17) has been evaluated against estrogen receptor-positive MCF-7 breast cancer cell lines. Molecular interactions and ADME stud...
Abstract Diabetes mellitus (DM) is the fastest growing metabolic disorder in the world. Recently,... more Abstract Diabetes mellitus (DM) is the fastest growing metabolic disorder in the world. Recently, more attention is paid to the study of natural products due to side effects of synthetic drugs. Stevia rebaudiana (Bertoni) is considered an encouraging starting point for the antidiabetic lead development. In the present study, the in vitro α-amylase inhibitory activity of the extracts of S. rebaudiana is investigated. In order to understand the molecular mechanism and future pharmacophore development, in silico study of secondary metabolites isolated from S. rebaudiana was carried out. Results indicated that water extract shows highest α-amylase inhibitory activity as compared to other extracts. Moreover, compound 20 (rebaudioside A) which has been previously reported and isolated from water extract showed the impressive binding profile with α-amylase. Therefore, our study suggests that S. rebaudiana could be used in the development of therapeutic drugs for the treatment of diabetes.
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