Cuproptosis, An Emerging Concept In The Field Of Diabetes Research, Presents A Novel And Promising Perspective For The Effective Management Of Diabetes Mellitus And Its Associated Complications. Diabetes, Characterized By Chronic Hyperglycemia, Poses A Substantial Global Health Burden, With An Increasing Prevalence Worldwide. Despite Significant Progress In Our Understanding Of This Complex Metabolic Disorder, Optimal Therapeutic Strategies Still Remain Elusive. The Advent Of Cuproptosis, A Term Coined To Describe Copper-Induced Cellular Cell Death And Its Pivotal Role In Diabetes Pathogenesis, Opens New Avenues For Innovative Interventions. Copper, An Indispensable Trace Element, Plays A Pivotal Role In A Myriad Of Vital Biological Processes, Encompassing Energy Production, Bolstering Antioxidant Defenses, And Altered Cellular Signaling. However, In The Context Of Diabetes, This Copper Homeostasis Is Perturbed, Driven By A Combination Of Genetic Predisposition, Dietary Patterns, And Environmental Factors. Excessive Copper Levels Act As Catalysts For Oxidative Stress, Sparking Intricate Intracellular Signaling Cascades That Further Exacerbate Metabolic Dysfunction. In This Review, We Aim To Explore The Interrelationship Between Copper And Diabetes Comprehensively, Shedding Light On The Intricate Mechanisms Underpinning Cuproptosis. By Unraveling The Roles Of Copper Transporters, Copper-Dependent Enzymes, And Cuproptotic Signaling Pathways, We Seek To Elucidate Potential Therapeutic Strategies That Harness The Power Of Copper Modulation In Diabetes Management. This Insight Sets The Stage For A Targeted Approach To Challenge The Complex Hurdles Posed By Diabetes, Potentially Transforming Our Therapeutic Strategies In The Ongoing Fight Against This Pervasive Global Health Concern.
{"title":"Copper Dyshomeostasis And Diabetic Complications: Chelation Strategies For Management.","authors":"Jahnavi Subramaniam, Aarya Aditi, Kishore Arumugam, Sathya Sri, Subramaniam Rajesh Bharathidevi, Kunka Mohanram Ramkumar","doi":"10.2174/0113895575308206240911104945","DOIUrl":"https://doi.org/10.2174/0113895575308206240911104945","url":null,"abstract":"<p><p>Cuproptosis, An Emerging Concept In The Field Of Diabetes Research, Presents A Novel And Promising Perspective For The Effective Management Of Diabetes Mellitus And Its Associated Complications. Diabetes, Characterized By Chronic Hyperglycemia, Poses A Substantial Global Health Burden, With An Increasing Prevalence Worldwide. Despite Significant Progress In Our Understanding Of This Complex Metabolic Disorder, Optimal Therapeutic Strategies Still Remain Elusive. The Advent Of Cuproptosis, A Term Coined To Describe Copper-Induced Cellular Cell Death And Its Pivotal Role In Diabetes Pathogenesis, Opens New Avenues For Innovative Interventions. Copper, An Indispensable Trace Element, Plays A Pivotal Role In A Myriad Of Vital Biological Processes, Encompassing Energy Production, Bolstering Antioxidant Defenses, And Altered Cellular Signaling. However, In The Context Of Diabetes, This Copper Homeostasis Is Perturbed, Driven By A Combination Of Genetic Predisposition, Dietary Patterns, And Environmental Factors. Excessive Copper Levels Act As Catalysts For Oxidative Stress, Sparking Intricate Intracellular Signaling Cascades That Further Exacerbate Metabolic Dysfunction. In This Review, We Aim To Explore The Interrelationship Between Copper And Diabetes Comprehensively, Shedding Light On The Intricate Mechanisms Underpinning Cuproptosis. By Unraveling The Roles Of Copper Transporters, Copper-Dependent Enzymes, And Cuproptotic Signaling Pathways, We Seek To Elucidate Potential Therapeutic Strategies That Harness The Power Of Copper Modulation In Diabetes Management. This Insight Sets The Stage For A Targeted Approach To Challenge The Complex Hurdles Posed By Diabetes, Potentially Transforming Our Therapeutic Strategies In The Ongoing Fight Against This Pervasive Global Health Concern.</p>","PeriodicalId":18548,"journal":{"name":"Mini reviews in medicinal chemistry","volume":" ","pages":""},"PeriodicalIF":3.3,"publicationDate":"2024-09-26","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142349871","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
This analytical mini-review focuses on the effects of trace elements, which includes Cu, Mn, Zn, and Se, as well as some rarer microelements, on the regulation of oxidative stress in the body and of certain diseases associated with it. Synergism and competition between certain microelements have been considered a hot topic in the applied molecular pharmacology of these specific bio-effects. Some ideas for further possible directions of research are expressed. Noteworthy, metal coordinating catalytical sites of certain enzymes function as pharmacophore-forming and connecting nanostructures. These sites can be regarded as targets for various effectors, making them pharmacologically significant contributors to biocatalysis.
{"title":"Trace Elements in Medicinal Metallomics.","authors":"Marina Orlova, Stepan Kalmykov, Tatiana Trofimova, Dmitry Kuznetsov","doi":"10.2174/0113895575333766240912162252","DOIUrl":"https://doi.org/10.2174/0113895575333766240912162252","url":null,"abstract":"<p><p>This analytical mini-review focuses on the effects of trace elements, which includes Cu, Mn, Zn, and Se, as well as some rarer microelements, on the regulation of oxidative stress in the body and of certain diseases associated with it. Synergism and competition between certain microelements have been considered a hot topic in the applied molecular pharmacology of these specific bio-effects. Some ideas for further possible directions of research are expressed. Noteworthy, metal coordinating catalytical sites of certain enzymes function as pharmacophore-forming and connecting nanostructures. These sites can be regarded as targets for various effectors, making them pharmacologically significant contributors to biocatalysis.</p>","PeriodicalId":18548,"journal":{"name":"Mini reviews in medicinal chemistry","volume":" ","pages":""},"PeriodicalIF":3.3,"publicationDate":"2024-09-25","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142349792","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2024-09-25DOI: 10.2174/0113895575300365240828065816
Justyna Żwawiak, Lucjusz Zaprutko, Anna Pawełczyk
Taxol is a compound with a rigid, tetracyclic structure of diterpene, which is characterized by significant antitumor properties. Firstly, Taxol has been isolated by extraction from the bark of the yew tree. However, the low level of availability obligated the researchers' world to uncover alternative techniques of Taxol obtainment. In the last few years, many synthetic and semi-synthetic methodologies have been elaborated. Nowadays, many novel biotechnological approaches using cell suspension cultures and biotransformation are initiated and expanded. These processes are very beneficial. The reason is that both the final product and the yield of the process have high levels. Such approaches are very distinctive and they help achieve significant quantities of natural compounds, which often exist in small amounts in plants. Moreover, a very important aspect of Taxol development is nanotechnology. The use of this method has many benefits - the retention time is protracted and the concentration of a drug in tumor tissue is raised. This is due to the specific targeting of nanomolecules. What is essential for patients is that systemic side effects are reduced and the healthy biological systems and tissues do not damage. Also, the paper presents new directions with the application of Artificial Intelligence methods. Every year, new concepts are created for obtaining Taxol and developing methods to significantly increase its bioavailability.
{"title":"Strategies in Taxol development. A review.","authors":"Justyna Żwawiak, Lucjusz Zaprutko, Anna Pawełczyk","doi":"10.2174/0113895575300365240828065816","DOIUrl":"https://doi.org/10.2174/0113895575300365240828065816","url":null,"abstract":"<p><p>Taxol is a compound with a rigid, tetracyclic structure of diterpene, which is characterized by significant antitumor properties. Firstly, Taxol has been isolated by extraction from the bark of the yew tree. However, the low level of availability obligated the researchers' world to uncover alternative techniques of Taxol obtainment. In the last few years, many synthetic and semi-synthetic methodologies have been elaborated. Nowadays, many novel biotechnological approaches using cell suspension cultures and biotransformation are initiated and expanded. These processes are very beneficial. The reason is that both the final product and the yield of the process have high levels. Such approaches are very distinctive and they help achieve significant quantities of natural compounds, which often exist in small amounts in plants. Moreover, a very important aspect of Taxol development is nanotechnology. The use of this method has many benefits - the retention time is protracted and the concentration of a drug in tumor tissue is raised. This is due to the specific targeting of nanomolecules. What is essential for patients is that systemic side effects are reduced and the healthy biological systems and tissues do not damage. Also, the paper presents new directions with the application of Artificial Intelligence methods. Every year, new concepts are created for obtaining Taxol and developing methods to significantly increase its bioavailability.</p>","PeriodicalId":18548,"journal":{"name":"Mini reviews in medicinal chemistry","volume":" ","pages":""},"PeriodicalIF":3.3,"publicationDate":"2024-09-25","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142365807","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
The statistical data related to cancer in recent years has shown a great increase in the number of cases and is likely to further increase in the future. Even after seeking thorough knowledge on the aetiology of cancer and related disorders and attempting to cure it by various methods like gene therapy, T cell therapy, chemotherapy, surgery, hormone therapy, and photodynamic therapy, there has always been disappointment concerning the survival rate. Hence, there is still a great urge for the discovery of novel drugs for the treatment of cancer. Chemotherapy being one of the widely used methods, several drug entities possessing anticancer properties are already in the market but none of them is known to show good efficacy which necessitates researchers to design newer drugs for the treatment of cancer. The urge to synthesize novel anticancer entities directed researchers towards molecular hybridization as one of the novel methods for designing newer drugs. Literature reveals wide research carried out on quinolin-2-one hybrids, possessing anticancer properties through different mechanisms. Tipifarnib and Dovitinib are quinolin-2-one hybrids used to treat cancer, possessing imidazole and benzimidazole heterocyclic rings. Different heterocyclic scaffolds such as pyrone, pyrrole, pyrimidine, pyridine, thiazole, and pyrazole in combination with heterocyclic quinolin-2-one have shown high potential to become lead for newer anticancer agents with better and wider therapeutic properties and lesser side effects. The current review presents information on the different quinolin-2-one hybrids and their effect on different cancer cell lines. It also imparts knowledge of the structural requirements for designing novel anticancer agents.
{"title":"Therapeutic Potental of Quinolin-2H-one Hybrids as Anticancer Agents.","authors":"Naik Soniya, Vasu Soumya, Mamle Desai Shivlingrao, M Manickavasagam, Chellappan Manickavasagam Meeramol","doi":"10.2174/0113895575305597240912192037","DOIUrl":"https://doi.org/10.2174/0113895575305597240912192037","url":null,"abstract":"<p><p>The statistical data related to cancer in recent years has shown a great increase in the number of cases and is likely to further increase in the future. Even after seeking thorough knowledge on the aetiology of cancer and related disorders and attempting to cure it by various methods like gene therapy, T cell therapy, chemotherapy, surgery, hormone therapy, and photodynamic therapy, there has always been disappointment concerning the survival rate. Hence, there is still a great urge for the discovery of novel drugs for the treatment of cancer. Chemotherapy being one of the widely used methods, several drug entities possessing anticancer properties are already in the market but none of them is known to show good efficacy which necessitates researchers to design newer drugs for the treatment of cancer. The urge to synthesize novel anticancer entities directed researchers towards molecular hybridization as one of the novel methods for designing newer drugs. Literature reveals wide research carried out on quinolin-2-one hybrids, possessing anticancer properties through different mechanisms. Tipifarnib and Dovitinib are quinolin-2-one hybrids used to treat cancer, possessing imidazole and benzimidazole heterocyclic rings. Different heterocyclic scaffolds such as pyrone, pyrrole, pyrimidine, pyridine, thiazole, and pyrazole in combination with heterocyclic quinolin-2-one have shown high potential to become lead for newer anticancer agents with better and wider therapeutic properties and lesser side effects. The current review presents information on the different quinolin-2-one hybrids and their effect on different cancer cell lines. It also imparts knowledge of the structural requirements for designing novel anticancer agents.</p>","PeriodicalId":18548,"journal":{"name":"Mini reviews in medicinal chemistry","volume":" ","pages":""},"PeriodicalIF":3.3,"publicationDate":"2024-09-25","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142349791","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2024-09-13DOI: 10.2174/0113895575297312240903055926
Sadat Shafi, Faraha Ahmed, Ayesha Waheed, Syed Sufiyan Ahmad, Sana Khan, Mohammad Ahmed Khan, Faheem Hyder Pottoo, Syed Arman Rabbani, Shailja Singh, Abul Kalam Najmi
Considerable advancements have been made in breast cancer therapeutics in the past few decades. However, the advent of chemo-resistance and adverse drug reactions coupled with tumor metastasis and recurrence posed a serious threat to combat this lethal disease. Novel anti-cancer agents, as well as new therapeutic strategies, are needed to complement conventional breast cancer therapies. The quest for developing novel anti-cancer drugs caused an upsurge in exploring and harnessing natural compounds, especially phytochemicals. Various research groups have explored and documented the anti-cancer potential of wide variety of phytochemical groups including flavonoids (curcumin, kaempferol, myricetin, quercetin, naringenin, apigenin, genistein epigallocatechin gallate), stilbenes (resveratrol), carotenoids (crocin, lycopene, lutein), and anthraquinone (Emodin). However, low chemical stability, poor water solubility, and short systemic half-life impede their clinical utility. The implication of nano-technological approaches to decode the pharmacokinetic challenges associated with phytochemical usage, as well as selective drug targeting, have markedly enhanced the pre-clinical anti-cancer activity, thus aiding in their clinical translation. This review documented the recent advances in utilizing phytochemicals for breast cancer prevention and lipidbased nanotechnological approaches for circumventing their pharmacokinetic concerns to enhance their systemic availability, cytotoxicity, and targeted delivery against breast cancer alone as well as in combination with conventional therapeutic agents.
{"title":"Phytochemicals and Nanotechnology: A Powerful Combination against Breast Cancer.","authors":"Sadat Shafi, Faraha Ahmed, Ayesha Waheed, Syed Sufiyan Ahmad, Sana Khan, Mohammad Ahmed Khan, Faheem Hyder Pottoo, Syed Arman Rabbani, Shailja Singh, Abul Kalam Najmi","doi":"10.2174/0113895575297312240903055926","DOIUrl":"https://doi.org/10.2174/0113895575297312240903055926","url":null,"abstract":"<p><p>Considerable advancements have been made in breast cancer therapeutics in the past few decades. However, the advent of chemo-resistance and adverse drug reactions coupled with tumor metastasis and recurrence posed a serious threat to combat this lethal disease. Novel anti-cancer agents, as well as new therapeutic strategies, are needed to complement conventional breast cancer therapies. The quest for developing novel anti-cancer drugs caused an upsurge in exploring and harnessing natural compounds, especially phytochemicals. Various research groups have explored and documented the anti-cancer potential of wide variety of phytochemical groups including flavonoids (curcumin, kaempferol, myricetin, quercetin, naringenin, apigenin, genistein epigallocatechin gallate), stilbenes (resveratrol), carotenoids (crocin, lycopene, lutein), and anthraquinone (Emodin). However, low chemical stability, poor water solubility, and short systemic half-life impede their clinical utility. The implication of nano-technological approaches to decode the pharmacokinetic challenges associated with phytochemical usage, as well as selective drug targeting, have markedly enhanced the pre-clinical anti-cancer activity, thus aiding in their clinical translation. This review documented the recent advances in utilizing phytochemicals for breast cancer prevention and lipidbased nanotechnological approaches for circumventing their pharmacokinetic concerns to enhance their systemic availability, cytotoxicity, and targeted delivery against breast cancer alone as well as in combination with conventional therapeutic agents.</p>","PeriodicalId":18548,"journal":{"name":"Mini reviews in medicinal chemistry","volume":" ","pages":""},"PeriodicalIF":3.3,"publicationDate":"2024-09-13","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142290916","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2024-08-19DOI: 10.2174/0113895575325210240805092741
Cahit Demirkiran, Seniz Demiryürek, Abdullah Tuncay Demiryürek
Sodium-Glucose Co-transporter-1/2 (SGLT1/2) inhibitors (also called glifozins) are a class of glucose-decreasing drugs in adults with Type 2 Diabetes (T2D). SGLT2 inhibitors diminish sodium and glucose reabsorption in the renal proximal convoluted tubule. Recent clinical trials have revealed that SGLT2 inhibitors might be beneficial for treating diseases other than diabetes, including chronic renal disease and Heart Failure (HF). Currently, SGLT2 inhibitors are recommended not only for the glycemic management of T2D but also for cardiovascular protection. SGLT2 inhibitors have become one of the foundational drugs for HF with reduced Ejection Fraction (HFrEF) treatment and the first medications with proven prognostic benefit in HF with preserved Ejection Fraction (HFpEF). At present, 11 SGLT1/2 inhibitors have been approved for clinical use in different countries. Beyond their anti-hyperglycemic effect, these inhibitors have shown clear cardio- and nephroprotective properties. A growing body of research studies suggests that SGLT1/2 inhibitors may provide potential clinical benefits in metabolic as well as oncological, hematological, and neurological disorders.
{"title":"Recent Progress and Perspectives in Sodium-Glucose Co-transporter 1/2 Inhibitors.","authors":"Cahit Demirkiran, Seniz Demiryürek, Abdullah Tuncay Demiryürek","doi":"10.2174/0113895575325210240805092741","DOIUrl":"https://doi.org/10.2174/0113895575325210240805092741","url":null,"abstract":"<p><p>Sodium-Glucose Co-transporter-1/2 (SGLT1/2) inhibitors (also called glifozins) are a class of glucose-decreasing drugs in adults with Type 2 Diabetes (T2D). SGLT2 inhibitors diminish sodium and glucose reabsorption in the renal proximal convoluted tubule. Recent clinical trials have revealed that SGLT2 inhibitors might be beneficial for treating diseases other than diabetes, including chronic renal disease and Heart Failure (HF). Currently, SGLT2 inhibitors are recommended not only for the glycemic management of T2D but also for cardiovascular protection. SGLT2 inhibitors have become one of the foundational drugs for HF with reduced Ejection Fraction (HFrEF) treatment and the first medications with proven prognostic benefit in HF with preserved Ejection Fraction (HFpEF). At present, 11 SGLT1/2 inhibitors have been approved for clinical use in different countries. Beyond their anti-hyperglycemic effect, these inhibitors have shown clear cardio- and nephroprotective properties. A growing body of research studies suggests that SGLT1/2 inhibitors may provide potential clinical benefits in metabolic as well as oncological, hematological, and neurological disorders.</p>","PeriodicalId":18548,"journal":{"name":"Mini reviews in medicinal chemistry","volume":" ","pages":""},"PeriodicalIF":3.3,"publicationDate":"2024-08-19","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142004593","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2024-04-30DOI: 10.2174/0113895575293447240424052516
Roshani Patil, Sanjay Sharma
Background: The National Health and Nutrition Examination Survey (NHANES) carried out a survey between 2007-10 and found that as compared to the general population, the prevalence of anemia in chronic kidney disease (CKD) patients was twice high. Daprodustat is an investigational novel drug for the treatment of renal anemia. Objective: The objective of this study is to provide a comprehensive review of chemistry, synthesis, pharmacology, pharmacokinetic, and bioanalytical methods for the analysis of Daprodustat. Methods: To improve understanding, a review was carried out by creating a database of relevant prior research from electronic sources such as ScienceDirect and PubMed. The methodology is shown in the flowchart of the literature selection process. Results: The drug was approved in 2020 for therapeutic purposes in Japan. It is a novel drug approved for the treatment of anemia in chronic kidney disease for oral administration. It is intended for adults who have undergone dialysis for a minimum of four months and are experiencing anemia as a result of chronic kidney disease. Conclusion: This review examines therapeutic, pharmacological, and analytical aspects related to the novel drug Daprodustat.
{"title":"Chemistry, Analysis, and Biological Aspects of Daprodustat, A New Hypoxia Inducible Factor Prolyl Hydroxylase Inhibitor: A Comprehensive Review","authors":"Roshani Patil, Sanjay Sharma","doi":"10.2174/0113895575293447240424052516","DOIUrl":"https://doi.org/10.2174/0113895575293447240424052516","url":null,"abstract":"Background: The National Health and Nutrition Examination Survey (NHANES) carried out a survey between 2007-10 and found that as compared to the general population, the prevalence of anemia in chronic kidney disease (CKD) patients was twice high. Daprodustat is an investigational novel drug for the treatment of renal anemia. Objective: The objective of this study is to provide a comprehensive review of chemistry, synthesis, pharmacology, pharmacokinetic, and bioanalytical methods for the analysis of Daprodustat. Methods: To improve understanding, a review was carried out by creating a database of relevant prior research from electronic sources such as ScienceDirect and PubMed. The methodology is shown in the flowchart of the literature selection process. Results: The drug was approved in 2020 for therapeutic purposes in Japan. It is a novel drug approved for the treatment of anemia in chronic kidney disease for oral administration. It is intended for adults who have undergone dialysis for a minimum of four months and are experiencing anemia as a result of chronic kidney disease. Conclusion: This review examines therapeutic, pharmacological, and analytical aspects related to the novel drug Daprodustat.","PeriodicalId":18548,"journal":{"name":"Mini reviews in medicinal chemistry","volume":"43 1","pages":""},"PeriodicalIF":3.8,"publicationDate":"2024-04-30","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140829260","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
: Skin is the largest organ of the human body functioning as a great primitive defensive barrier against different harmful environmental factors. However, it is damaged through varying injuries such as different wounds, burns, and skin cancers that cause disruption in internal organs and essential mechanisms of the body through inflammation, oxidation, coagulation problems, infection, etc. Melatonin is the major hormone of the pineal gland that is also effective in skin disorders due to strong antioxidant and anti-inflammatory features with additional desirable antiapoptotic, anti-cancer, and antibiotic properties. However, melatonin characteristics require improvements due to its limited water solubility, halflife and stability. The application of nanocarrier systems can improve its solubility, permeability, and efficiency, as well as inhibit its degradation and promote photostability. Our main purpose in the current review is to explore the possible role of melatonin and melatonin-containing nanocarriers in skin disorders focused on wounds. Additionally, melatonin’s effect in regenerative medicine and its structures as a wound dressing in skin damage has been considered.
{"title":"Evaluation of Melatonin and its Nanostructures Effects on Skin Disorders Focused on Wound Healing","authors":"Seyedeh Mohaddeseh Mousavi, Leila Etemad, Davood Yari, Maryam Hashemi, Zahra Salmasi","doi":"10.2174/0113895575299255240422055203","DOIUrl":"https://doi.org/10.2174/0113895575299255240422055203","url":null,"abstract":": Skin is the largest organ of the human body functioning as a great primitive defensive barrier against different harmful environmental factors. However, it is damaged through varying injuries such as different wounds, burns, and skin cancers that cause disruption in internal organs and essential mechanisms of the body through inflammation, oxidation, coagulation problems, infection, etc. Melatonin is the major hormone of the pineal gland that is also effective in skin disorders due to strong antioxidant and anti-inflammatory features with additional desirable antiapoptotic, anti-cancer, and antibiotic properties. However, melatonin characteristics require improvements due to its limited water solubility, halflife and stability. The application of nanocarrier systems can improve its solubility, permeability, and efficiency, as well as inhibit its degradation and promote photostability. Our main purpose in the current review is to explore the possible role of melatonin and melatonin-containing nanocarriers in skin disorders focused on wounds. Additionally, melatonin’s effect in regenerative medicine and its structures as a wound dressing in skin damage has been considered.","PeriodicalId":18548,"journal":{"name":"Mini reviews in medicinal chemistry","volume":"10 1","pages":""},"PeriodicalIF":3.8,"publicationDate":"2024-04-30","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140829425","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2024-04-27DOI: 10.2174/0113895575301011240407082559
Nelofer Ereej, Huma Hameed, Mahtab Ahmad Khan, Saleha Faheem, Anam Hameed
:: Neurological disorders present a formidable challenge in modern medicine due to the intricate obstacles set for the brain and the multipart nature of genetic interventions. This review article delves into the promising realm of nanoparticle-based gene therapy as an innovative approach to addressing the intricacies of neurological disorders. Nanoparticles (NPs) provide a multipurpose podium for the conveyance of therapeutic genes, offering unique properties such as precise targeting, enhanced stability, and the potential to bypass blood-brain barrier (BBB) restrictions. This comprehensive exploration reviews the current state of nanoparticle-mediated gene therapy in neurological disorders, highlighting recent advancements and breakthroughs. The discussion encompasses the synthesis of nanoparticles from various materials and their conjugation to therapeutic genes, emphasizing the flexibility in design that contributes to specific tissue targeting. The abstract also addresses the low immunogenicity of these nanoparticles and their stability in circulation, critical factors for successful gene delivery. While the potential of NP-based gene therapy for neurological disorders is vast, challenges and gaps in knowledge persist. The lack of extensive clinical trials leaves questions about safety and potential side effects unanswered. Therefore, this abstract emphasizes the need for further research to validate the therapeutic applications of NP-mediated gene therapy and to address nanosafety concerns. In conclusion, nanoparticle-based gene therapy emerges as a promising avenue in the pursuit of effective treatments for neurological disorders. This abstract advocates for continued research efforts to bridge existing knowledge gaps, unlocking the full potential of this innovative approach and paving the way for transformative solutions in the realm of neurological health.
{"title":"Nanoparticle-based Gene Therapy for Neurodegenerative Disorders","authors":"Nelofer Ereej, Huma Hameed, Mahtab Ahmad Khan, Saleha Faheem, Anam Hameed","doi":"10.2174/0113895575301011240407082559","DOIUrl":"https://doi.org/10.2174/0113895575301011240407082559","url":null,"abstract":":: Neurological disorders present a formidable challenge in modern medicine due to the intricate obstacles set for the brain and the multipart nature of genetic interventions. This review article delves into the promising realm of nanoparticle-based gene therapy as an innovative approach to addressing the intricacies of neurological disorders. Nanoparticles (NPs) provide a multipurpose podium for the conveyance of therapeutic genes, offering unique properties such as precise targeting, enhanced stability, and the potential to bypass blood-brain barrier (BBB) restrictions. This comprehensive exploration reviews the current state of nanoparticle-mediated gene therapy in neurological disorders, highlighting recent advancements and breakthroughs. The discussion encompasses the synthesis of nanoparticles from various materials and their conjugation to therapeutic genes, emphasizing the flexibility in design that contributes to specific tissue targeting. The abstract also addresses the low immunogenicity of these nanoparticles and their stability in circulation, critical factors for successful gene delivery. While the potential of NP-based gene therapy for neurological disorders is vast, challenges and gaps in knowledge persist. The lack of extensive clinical trials leaves questions about safety and potential side effects unanswered. Therefore, this abstract emphasizes the need for further research to validate the therapeutic applications of NP-mediated gene therapy and to address nanosafety concerns. In conclusion, nanoparticle-based gene therapy emerges as a promising avenue in the pursuit of effective treatments for neurological disorders. This abstract advocates for continued research efforts to bridge existing knowledge gaps, unlocking the full potential of this innovative approach and paving the way for transformative solutions in the realm of neurological health.","PeriodicalId":18548,"journal":{"name":"Mini reviews in medicinal chemistry","volume":"54 1","pages":""},"PeriodicalIF":3.8,"publicationDate":"2024-04-27","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140812611","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2024-04-27DOI: 10.2174/0113895575308674240415074629
Kihang Choi
: Drug-like properties play pivotal roles in drug adsorption, distribution, metabolism, excretion, and toxicity. Therefore, efficiently optimizing these properties is essential for the successful development of novel therapeutics. Understanding the structure–property relationships of clinically approved drugs can provide valuable insights for drug design and optimization strategies. Among the new drugs approved in 2023, which include 31 small-molecule drugs in the US, the structure-property relationships of nine drugs were compiled from the medicinal chemistry literature, in which detailed information on pharmacokinetic and/or physicochemical properties was reported not only for the final drug but also for its key analogs generated during drug development. The structure-property relationships of nine newly approved drugs are summarized, including three kinase inhibitors and three G-protein-coupled receptor antagonists. Several optimization strategies, such as bioisosteric replacement and steric handle installation, have successfully produced clinical candidates with enhanced physicochemical and pharmacokinetic properties. The summarized structure–property relationships demonstrate how appropriate structural modifications can effectively improve overall drug-like properties. The ongoing exploration of structure– property relationships of clinically approved drugs is expected to offer valuable guidance for developing future drugs.
:类药物特性在药物吸附、分布、代谢、排泄和毒性方面起着关键作用。因此,有效优化这些性质对于成功开发新型疗法至关重要。了解临床批准药物的结构-性质关系可为药物设计和优化策略提供宝贵的见解。2023 年美国批准的新药包括 31 种小分子药物,在这些药物中,有 9 种药物的结构-性质关系是从药物化学文献中整理出来的,这些文献不仅报道了最终药物的药代动力学和/或理化性质的详细信息,还报道了药物开发过程中产生的关键类似物的信息。本文总结了九种新批准药物的结构-性质关系,包括三种激酶抑制剂和三种 G 蛋白偶联受体拮抗剂。几种优化策略,如生物异构替代和立体柄安装,成功地开发出了具有更好理化和药代动力学特性的临床候选药物。总结出的结构-性质关系表明,适当的结构修饰可以有效改善药物的整体类似性质。对临床批准药物的结构-性质关系的不断探索有望为未来药物的开发提供有价值的指导。
{"title":"Structure-property Relationships Reported for the New Drugs Approved in 2023","authors":"Kihang Choi","doi":"10.2174/0113895575308674240415074629","DOIUrl":"https://doi.org/10.2174/0113895575308674240415074629","url":null,"abstract":": Drug-like properties play pivotal roles in drug adsorption, distribution, metabolism, excretion, and toxicity. Therefore, efficiently optimizing these properties is essential for the successful development of novel therapeutics. Understanding the structure–property relationships of clinically approved drugs can provide valuable insights for drug design and optimization strategies. Among the new drugs approved in 2023, which include 31 small-molecule drugs in the US, the structure-property relationships of nine drugs were compiled from the medicinal chemistry literature, in which detailed information on pharmacokinetic and/or physicochemical properties was reported not only for the final drug but also for its key analogs generated during drug development. The structure-property relationships of nine newly approved drugs are summarized, including three kinase inhibitors and three G-protein-coupled receptor antagonists. Several optimization strategies, such as bioisosteric replacement and steric handle installation, have successfully produced clinical candidates with enhanced physicochemical and pharmacokinetic properties. The summarized structure–property relationships demonstrate how appropriate structural modifications can effectively improve overall drug-like properties. The ongoing exploration of structure– property relationships of clinically approved drugs is expected to offer valuable guidance for developing future drugs.","PeriodicalId":18548,"journal":{"name":"Mini reviews in medicinal chemistry","volume":"7 1","pages":""},"PeriodicalIF":3.8,"publicationDate":"2024-04-27","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140812894","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}