Background: Oxadiazole derivatives have shown significant potential as anti-cancer agents with low μM potencies. Some examples of drugs in this class include Raltegravir, Zibotentan, Setileuton (MK-0633), Nesapidil, Furamizole, and Tidazosin. The presence of the oxadiazole nucleus in Raltegravir exemplifies its importance in drug development, showcasing how specific structural motifs like oxadiazole can be strategically incorporated into molecules to achieve desired therapeutic effects. A large number of researchers across the globe have already developed and reported many oxadiazoles as potential anti-cancer medicines. Objective: Therefore, we tried to discuss the anti-cancer potentials of oxadiazole derivatives reported between 2019 and 2023. The design strategies, structure-activity relationship (SAR), and protein- inhibitor interactions of potential compounds on different targets have to be identified to help the medicinal chemists design new drug-likeness oxadiazole molecules for anti-cancer therapy. Similarly, the ADMET profiles of potential oxadiazoles using the in silico SWISSADME tool have to be studied. Results: We have highlighted the recently reported most potent oxadiazole derivatives as well as their hybrid compounds. The SAR study revealed that oxadiazole-linked pyridine, indazole, thiadiazine, quinoxaline, thiazolidine, indeno-pyrazole, thiophene, piperidine, benzimidazole, triazole, and sulphonamide showcased promising anti-cancer action. The chemico-biological interactions of potential oxadiazole compounds suggest good interactions with different amino acid residues that make them possible candidates for developing novel and effective anti-cancer therapies. Similarly, the in silico ADMET report suggested favourable physicochemical, pharmacokinetic, and druglikeness properties of potential oxadiazole compounds. Conclusion: Overall, these results will prove to be a helpful and vital tool for medicinal chemists investigating and working with oxadiazoles for anti-cancer action.
{"title":"Unveiling the Anti-cancer Potential of Oxadiazole Derivatives: A Comprehensive Exploration of Structure-Activity Relationships and Chemico-Biological Insights","authors":"Sai Satyaprakash Mishra, Ajeya Samanta, Abhik Paul, Avik Maji, Tapan Kumar Maity","doi":"10.2174/0115734064329573240823113924","DOIUrl":"https://doi.org/10.2174/0115734064329573240823113924","url":null,"abstract":"Background: Oxadiazole derivatives have shown significant potential as anti-cancer agents with low μM potencies. Some examples of drugs in this class include Raltegravir, Zibotentan, Setileuton (MK-0633), Nesapidil, Furamizole, and Tidazosin. The presence of the oxadiazole nucleus in Raltegravir exemplifies its importance in drug development, showcasing how specific structural motifs like oxadiazole can be strategically incorporated into molecules to achieve desired therapeutic effects. A large number of researchers across the globe have already developed and reported many oxadiazoles as potential anti-cancer medicines. Objective: Therefore, we tried to discuss the anti-cancer potentials of oxadiazole derivatives reported between 2019 and 2023. The design strategies, structure-activity relationship (SAR), and protein- inhibitor interactions of potential compounds on different targets have to be identified to help the medicinal chemists design new drug-likeness oxadiazole molecules for anti-cancer therapy. Similarly, the ADMET profiles of potential oxadiazoles using the in silico SWISSADME tool have to be studied. Results: We have highlighted the recently reported most potent oxadiazole derivatives as well as their hybrid compounds. The SAR study revealed that oxadiazole-linked pyridine, indazole, thiadiazine, quinoxaline, thiazolidine, indeno-pyrazole, thiophene, piperidine, benzimidazole, triazole, and sulphonamide showcased promising anti-cancer action. The chemico-biological interactions of potential oxadiazole compounds suggest good interactions with different amino acid residues that make them possible candidates for developing novel and effective anti-cancer therapies. Similarly, the in silico ADMET report suggested favourable physicochemical, pharmacokinetic, and druglikeness properties of potential oxadiazole compounds. Conclusion: Overall, these results will prove to be a helpful and vital tool for medicinal chemists investigating and working with oxadiazoles for anti-cancer action.","PeriodicalId":18382,"journal":{"name":"Medicinal Chemistry","volume":"8 1","pages":""},"PeriodicalIF":2.3,"publicationDate":"2024-09-02","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142219126","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2024-09-02DOI: 10.2174/0115734064328915240827062052
Neetu Agrawal, Deepika Goyal, Shilpi Pathak
Thiazine, a six-membered heterocycle containing nitrogen and sulfur atoms, is of paramount importance due to its diverse biological functions and broad therapeutic effects. The pharmacological attributes of 1,3-thiazine span a wide range of activities, including antileukemic, antimycobacterial, anti-inflammatory, sedative, hypnotic, anti-influenza, antituberculosis, melanogenesis inhibition, BACE1 inhibition (with anti-Alzheimer's potential), growth promotion, neuroprotective, and anticonvulsant properties. Consequently, novel synthetic methodologies and the design of new 1,3-thiazine derivatives are significantly influenced by recent research findings. This comprehensive review explores both in vivo and in vitro preclinical studies on the biomedical and therapeutic applications of 1,3-thiazine, highlighting its extensive medical relevance. It is anticipated that derivatization strategies for 1,3-thiazine will open new avenues for the development of innovative biological agents. This review aims to engage researchers, stimulating the creation of promising new treatments and preventive measures for various diseases.
{"title":"Exploring the Diverse Therapeutic Applications of 1, 3-Thiazine: A Comprehensive Review","authors":"Neetu Agrawal, Deepika Goyal, Shilpi Pathak","doi":"10.2174/0115734064328915240827062052","DOIUrl":"https://doi.org/10.2174/0115734064328915240827062052","url":null,"abstract":"Thiazine, a six-membered heterocycle containing nitrogen and sulfur atoms, is of paramount importance due to its diverse biological functions and broad therapeutic effects. The pharmacological attributes of 1,3-thiazine span a wide range of activities, including antileukemic, antimycobacterial, anti-inflammatory, sedative, hypnotic, anti-influenza, antituberculosis, melanogenesis inhibition, BACE1 inhibition (with anti-Alzheimer's potential), growth promotion, neuroprotective, and anticonvulsant properties. Consequently, novel synthetic methodologies and the design of new 1,3-thiazine derivatives are significantly influenced by recent research findings. This comprehensive review explores both in vivo and in vitro preclinical studies on the biomedical and therapeutic applications of 1,3-thiazine, highlighting its extensive medical relevance. It is anticipated that derivatization strategies for 1,3-thiazine will open new avenues for the development of innovative biological agents. This review aims to engage researchers, stimulating the creation of promising new treatments and preventive measures for various diseases.","PeriodicalId":18382,"journal":{"name":"Medicinal Chemistry","volume":"27 1","pages":""},"PeriodicalIF":2.3,"publicationDate":"2024-09-02","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142219125","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2024-09-02DOI: 10.2174/0115734064317811240815184525
Tanzeel Ur Rehman, Yaser Abdulaziz Alnaam, Misbah Zahid, Jari S. Algethami
Aim: Due to interdisciplinary research, many innovative concepts have been merged that seemed to be impractical. Recently, medicinal organometallic chemistry has made remarkable progress, but the latency of these compounds has not been fully exploited. This systematic review has examined the published literature on anticancer organometallic chemistry across countries, science fields, and organizations involved in organometallics research for cancer. Method: The study data related to anticancer organometallics were searched from Scopus between 2085 and 2022. Biblioshiny and VOS Viewers were used to analyze and visualize patterns in scientific literature derived from Scopus. Results: Publications on organometallic compounds have been found to contribute to, on average, 1.02% per year, accounting for 94.3% of the total scholarly work published in the last two decades since 2003. However, research productivity has been found to be steadily improved, with 81.5% of all publications produced between 2011 and 2022. The countries possessing the highest published work have been found to be China, the UK, and Germany. The leading institutions, the University of Warwick, United Kingdom, and the University of Auckland, New Zealand, have topped the list of organizations with the most publications. Although the use of medicinal organometallics for cancer has become widespread over the last two decennaries, there has been a notable influx of groundbreaking scientific publications in recent years. Conclusion: The findings of this study may enable researchers to envision potential future scenarios for scientific collaborations involving the utilization of organometallics in the treatment of cancer. This study may provide aspiring and current researchers with the necessary tools and knowledge to effectively pursue their research endeavors for scientific collaborations investigating the use of anticancer organometallics in the medicinal field. The areas, such as ruthenium with reactive oxygen species and angiogenesis, represent opportunities for future investigation and innovation.
{"title":"Mapping the Landscape of Global Anticancer Organometallics Research: A Systematic Review","authors":"Tanzeel Ur Rehman, Yaser Abdulaziz Alnaam, Misbah Zahid, Jari S. Algethami","doi":"10.2174/0115734064317811240815184525","DOIUrl":"https://doi.org/10.2174/0115734064317811240815184525","url":null,"abstract":"Aim: Due to interdisciplinary research, many innovative concepts have been merged that seemed to be impractical. Recently, medicinal organometallic chemistry has made remarkable progress, but the latency of these compounds has not been fully exploited. This systematic review has examined the published literature on anticancer organometallic chemistry across countries, science fields, and organizations involved in organometallics research for cancer. Method: The study data related to anticancer organometallics were searched from Scopus between 2085 and 2022. Biblioshiny and VOS Viewers were used to analyze and visualize patterns in scientific literature derived from Scopus. Results: Publications on organometallic compounds have been found to contribute to, on average, 1.02% per year, accounting for 94.3% of the total scholarly work published in the last two decades since 2003. However, research productivity has been found to be steadily improved, with 81.5% of all publications produced between 2011 and 2022. The countries possessing the highest published work have been found to be China, the UK, and Germany. The leading institutions, the University of Warwick, United Kingdom, and the University of Auckland, New Zealand, have topped the list of organizations with the most publications. Although the use of medicinal organometallics for cancer has become widespread over the last two decennaries, there has been a notable influx of groundbreaking scientific publications in recent years. Conclusion: The findings of this study may enable researchers to envision potential future scenarios for scientific collaborations involving the utilization of organometallics in the treatment of cancer. This study may provide aspiring and current researchers with the necessary tools and knowledge to effectively pursue their research endeavors for scientific collaborations investigating the use of anticancer organometallics in the medicinal field. The areas, such as ruthenium with reactive oxygen species and angiogenesis, represent opportunities for future investigation and innovation.","PeriodicalId":18382,"journal":{"name":"Medicinal Chemistry","volume":"20 1","pages":""},"PeriodicalIF":2.3,"publicationDate":"2024-09-02","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142219129","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2024-09-02DOI: 10.2174/0115734064327558240826050650
Irena Kostova
: Although platinum and ruthenium complexes have been clinically recognized to be the most efficient metal-based anticancer candidates, applied in a wide range of cancer cell lines, their serious toxic effects and drug resistance require the necessity for new metal antitumor complexes. There is excessive interest in the design of new Pt-group metal complexes, including osmium and rhodium, which have revealed great chemotherapeutic potential. They have demonstrated modes of action that differ from those of the most broadly-used in clinical practice platinum- and rutheniumbased compounds. Os and Rh complexes are equipotent to their platinum and ruthenium analogues. Many Os- and Rh-based complexes with strong antitumor activity and low toxic effects have been developed and recognized for their antineoplastic activity in the last few years. Some of them have exposed different action profiles from the conventional anticancer metal complexes. That is why they might serve as a possible alternative that deserves more investigation, though limited studies on their biological effects have been reported, which is in contrast with the classical isoelectronic Pt and Ru complex compounds. Studies of Os and Rh complexes are currently attracting scientific attention. Recent developments of this interesting class of novel chemotherapeutic agents have been reviewed.
{"title":"Recent Advances in Anticancer Research of Osmium and Rhodium Complexes","authors":"Irena Kostova","doi":"10.2174/0115734064327558240826050650","DOIUrl":"https://doi.org/10.2174/0115734064327558240826050650","url":null,"abstract":": Although platinum and ruthenium complexes have been clinically recognized to be the most efficient metal-based anticancer candidates, applied in a wide range of cancer cell lines, their serious toxic effects and drug resistance require the necessity for new metal antitumor complexes. There is excessive interest in the design of new Pt-group metal complexes, including osmium and rhodium, which have revealed great chemotherapeutic potential. They have demonstrated modes of action that differ from those of the most broadly-used in clinical practice platinum- and rutheniumbased compounds. Os and Rh complexes are equipotent to their platinum and ruthenium analogues. Many Os- and Rh-based complexes with strong antitumor activity and low toxic effects have been developed and recognized for their antineoplastic activity in the last few years. Some of them have exposed different action profiles from the conventional anticancer metal complexes. That is why they might serve as a possible alternative that deserves more investigation, though limited studies on their biological effects have been reported, which is in contrast with the classical isoelectronic Pt and Ru complex compounds. Studies of Os and Rh complexes are currently attracting scientific attention. Recent developments of this interesting class of novel chemotherapeutic agents have been reviewed.","PeriodicalId":18382,"journal":{"name":"Medicinal Chemistry","volume":"167 1","pages":""},"PeriodicalIF":2.3,"publicationDate":"2024-09-02","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142219127","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2024-08-29DOI: 10.2174/0115734064314933240812120123
Sony A.S., Xavier Suresh
Background: Flavonoids express a wide range of medicinal properties, our study presented results on the anticancer activity of selected compounds using in silico studies. Objective: In this article, in silico studies were carried out to find promising anticancer lead among selected flavonoid compounds. Methods: Here, we carried out molecular docking and MD simulation for anticancer screening of flavonoid derivatives against CDK2 and CDK9 proteins. Results: Among the compounds under investigation, Flavone and Recoflavone had the lowest binding energy against CDK2/CDK9 targets using docking studies and MD simulations. Conclusion: We can conclude that Flavone and Recoflavone are promising anticancer lead compounds in the development of new anticancer drugs.
{"title":"Docking and Molecular Dynamics Studies on Anticancer Activities of Flavonoids as Inhibitors of CDK2 and CDK9","authors":"Sony A.S., Xavier Suresh","doi":"10.2174/0115734064314933240812120123","DOIUrl":"https://doi.org/10.2174/0115734064314933240812120123","url":null,"abstract":"Background: Flavonoids express a wide range of medicinal properties, our study presented results on the anticancer activity of selected compounds using in silico studies. Objective: In this article, in silico studies were carried out to find promising anticancer lead among selected flavonoid compounds. Methods: Here, we carried out molecular docking and MD simulation for anticancer screening of flavonoid derivatives against CDK2 and CDK9 proteins. Results: Among the compounds under investigation, Flavone and Recoflavone had the lowest binding energy against CDK2/CDK9 targets using docking studies and MD simulations. Conclusion: We can conclude that Flavone and Recoflavone are promising anticancer lead compounds in the development of new anticancer drugs.","PeriodicalId":18382,"journal":{"name":"Medicinal Chemistry","volume":"13 1","pages":""},"PeriodicalIF":2.3,"publicationDate":"2024-08-29","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142219128","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2024-08-28DOI: 10.2174/0115734064315601240628115330
Md. Abdullah Al Mashud, Ramprosad Devnath, Masuma Anzuman, Mahbuba Iasmin Sumona, Md. Shamim Hossain, Ajoy Kumer, Md. Enamul Kabir Talukder, Md. Mashiar Rahman, Raihan Rahman Imon, Shopnil Akash, Abdelfattah El Moussaoui, Ahmad Mohammad Salamatullah, Mohammed Bourhia
Background: Head and neck cancer (HNC) is on the rise worldwide, endangering lives and straining healthcare systems in both developing and developed nations. Despite the availability of a number of therapy options, the success rate for treating and controlling head and neck cancer remains dismal. To combat the aggressiveness and drug resistance of Epstein-Barr virus (EBV)-positive Head-Neck cancer cells, this study looks into the potential of Euphorbia tirucalli (pencil cactus) leaf extract. Objectives: The goal of this study is to identify prospective therapeutic candidates from the extract of Euphorbia tirucalli (pencil cactus) leaves, which have the ability to inhibit Epstein-Barr virus (EBV)-positive Head-Neck cancer cells. Materials and Methods: The thirteen most important chemical components found in Euphorbia tirucalli (pencil cactus) leaves were analyzed by means of molecular modeling techniques such as Absorption, Distribution, Metabolism, Excretion, and Toxicity (ADMET), Quantum Mechanics (QM) calculation, Molecular Dynamics (MD) profiling, molecular docking, and molecular dynamics (MD) simulations. Using the Prediction of Activity Spectra for Substances (PASS) model, we assess the potency of these compounds in vitro against an Epstein- Barr virus (EBV)-positive head-neck cancer cell line. Important molecular properties such as chemical potential, electronegativity, hardness, and softness can be determined with the use of quantum chemical calculations employing HOMO-LUMO analysis. These drugs' safety and toxicological characteristics are better understood thanks to assessments of their pharmacokinetics and ADMET. These tests show that there is no risk of hepatotoxicity or cancer in humans and that they are safe to use. In order to verify binding interactions and complex stability, molecular dynamics simulations are used to reveal stable docked complexes. Results: The molecular docking analysis identifies ligands (01), (02), and (10) as strong competitors, with strong binding affinity for the Epstein-Barr virus (EBV)-positive Head-Neck cancer cell line. Not only do the ligands (01), (02), and (10) match the criteria for a potential new inhibitor of head-neck cancer, but they also outperform the present FDA-approved treatment. Conclusion: Taraxerol, euphol, and ephorginol, three phytochemicals isolated from the leaves of the Euphorbia tirucalli (pencil cactus), have been identified as effective anti-cancer agents with the potential to serve as a foundation for novel head-neck cancer therapies, particularly those targeting the Epstein-Barr virus (EBV)-overexpressing subtype of this disease. An effective, individualized treatment plan for head-neck cancer is a long way off, but this study is a major step forward that could change the lives of patients and lessen the global burden of this disease.
{"title":"New Approach as Inhibitor Against Head-Neck Cancer by In silico, DFT, FMOs, Docking, Molecular Dynamic, and ADMET of Euphorbia tirucalli (Pencil Cactus)","authors":"Md. Abdullah Al Mashud, Ramprosad Devnath, Masuma Anzuman, Mahbuba Iasmin Sumona, Md. Shamim Hossain, Ajoy Kumer, Md. Enamul Kabir Talukder, Md. Mashiar Rahman, Raihan Rahman Imon, Shopnil Akash, Abdelfattah El Moussaoui, Ahmad Mohammad Salamatullah, Mohammed Bourhia","doi":"10.2174/0115734064315601240628115330","DOIUrl":"https://doi.org/10.2174/0115734064315601240628115330","url":null,"abstract":"Background: Head and neck cancer (HNC) is on the rise worldwide, endangering lives and straining healthcare systems in both developing and developed nations. Despite the availability of a number of therapy options, the success rate for treating and controlling head and neck cancer remains dismal. To combat the aggressiveness and drug resistance of Epstein-Barr virus (EBV)-positive Head-Neck cancer cells, this study looks into the potential of Euphorbia tirucalli (pencil cactus) leaf extract. Objectives: The goal of this study is to identify prospective therapeutic candidates from the extract of Euphorbia tirucalli (pencil cactus) leaves, which have the ability to inhibit Epstein-Barr virus (EBV)-positive Head-Neck cancer cells. Materials and Methods: The thirteen most important chemical components found in Euphorbia tirucalli (pencil cactus) leaves were analyzed by means of molecular modeling techniques such as Absorption, Distribution, Metabolism, Excretion, and Toxicity (ADMET), Quantum Mechanics (QM) calculation, Molecular Dynamics (MD) profiling, molecular docking, and molecular dynamics (MD) simulations. Using the Prediction of Activity Spectra for Substances (PASS) model, we assess the potency of these compounds in vitro against an Epstein- Barr virus (EBV)-positive head-neck cancer cell line. Important molecular properties such as chemical potential, electronegativity, hardness, and softness can be determined with the use of quantum chemical calculations employing HOMO-LUMO analysis. These drugs' safety and toxicological characteristics are better understood thanks to assessments of their pharmacokinetics and ADMET. These tests show that there is no risk of hepatotoxicity or cancer in humans and that they are safe to use. In order to verify binding interactions and complex stability, molecular dynamics simulations are used to reveal stable docked complexes. Results: The molecular docking analysis identifies ligands (01), (02), and (10) as strong competitors, with strong binding affinity for the Epstein-Barr virus (EBV)-positive Head-Neck cancer cell line. Not only do the ligands (01), (02), and (10) match the criteria for a potential new inhibitor of head-neck cancer, but they also outperform the present FDA-approved treatment. Conclusion: Taraxerol, euphol, and ephorginol, three phytochemicals isolated from the leaves of the Euphorbia tirucalli (pencil cactus), have been identified as effective anti-cancer agents with the potential to serve as a foundation for novel head-neck cancer therapies, particularly those targeting the Epstein-Barr virus (EBV)-overexpressing subtype of this disease. An effective, individualized treatment plan for head-neck cancer is a long way off, but this study is a major step forward that could change the lives of patients and lessen the global burden of this disease.","PeriodicalId":18382,"journal":{"name":"Medicinal Chemistry","volume":"115 1","pages":""},"PeriodicalIF":2.3,"publicationDate":"2024-08-28","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142219151","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2024-08-26DOI: 10.2174/0115734064324855240806052735
Jose Manuel Mendez-Arriaga
Background: Globally, parasitic diseases are considered among the neglected diseases. Clinically, several drugs are used in treatment, however due to drug resistance and multidrug resistance and the low investment in new research lines, there has been a failure in the treatment of parasitic illnesses. Objectives: The present mini-review is a comprehensive review of the use of platinum group metals as biological agents. It aims to establish the actual state of the art of these metal elements in the antiparasitic activity-specific area and define the future possibilities of action. Methods: The review comprises more than 100 research works done in this field. The differences between platinum group metals chemistry and their use as metal complexes with biological activity have been discussed. Results: This review highlighted the platinum group metal's potential as an antiparasitic agent for different diseases. Conclusion: The review will be helpful for the researchers involved in targeted drugs for parasitic disease therapy.
{"title":"Platinum Group Metals against Parasites: State of the Art and Future Perspectives","authors":"Jose Manuel Mendez-Arriaga","doi":"10.2174/0115734064324855240806052735","DOIUrl":"https://doi.org/10.2174/0115734064324855240806052735","url":null,"abstract":"Background: Globally, parasitic diseases are considered among the neglected diseases. Clinically, several drugs are used in treatment, however due to drug resistance and multidrug resistance and the low investment in new research lines, there has been a failure in the treatment of parasitic illnesses. Objectives: The present mini-review is a comprehensive review of the use of platinum group metals as biological agents. It aims to establish the actual state of the art of these metal elements in the antiparasitic activity-specific area and define the future possibilities of action. Methods: The review comprises more than 100 research works done in this field. The differences between platinum group metals chemistry and their use as metal complexes with biological activity have been discussed. Results: This review highlighted the platinum group metal's potential as an antiparasitic agent for different diseases. Conclusion: The review will be helpful for the researchers involved in targeted drugs for parasitic disease therapy.","PeriodicalId":18382,"journal":{"name":"Medicinal Chemistry","volume":"18 1","pages":""},"PeriodicalIF":2.3,"publicationDate":"2024-08-26","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142219154","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2024-08-12DOI: 10.2174/0115734064316022240801093905
Hoang Minh Phan, Tan Thanh Mai, Thinh Nguyen Quang Don, Dat Thanh Do, Khac Minh Thai, Thanh Dao Tran, Phuong Truong, Phuong Nguyen Hoai Huynh
Introduction: Chalcone compounds exhibit diverse bioactivities, attracting significant interest. Morpholine is a heterocycle commonly used in medicinal chemistry. It could enhance the potency, pharmacokinetics, and bioactivities of its compounds. Method: Adding morpholine into the chalcone scaffold could help create new compounds with favorable bioactivities. In this study, a new parallel synthesis procedure has been developed. Using this procedure, 18 novel morpholinoalkoxychalcones have been successfully synthesized. They had chains with morpholine appended on ring A or ring B. All the synthesized compounds were evaluated for the antibacterial and antifungal activities by agar diffusion method on 5 bacteria and 2 fungi strains. Results: The compounds with good inhibition were determined with respect to the MIC values by the agar dilution method. Among the tested compounds, B.21 was found to be the best against S. faecalis, with an MIC value of 0.6 mM. B.43 was found to be the best against A. niger and C. albicans with MIC value of 2.04 mM. Conclusion: The in silico study has revealed two targets to align with the in vitro results. Longer alkyl chains have enhanced the activity, along with the presence of OH, NH2, and halogen groups on both rings A and B. result: We synthesis 18 new morpholinoalkoxychalcones with the chain both on ring A and ring B. All compounds are new based on Scifinder at 10/2023. 3 compounds showed intermediate activity on 5 bacteria strains and 8 compounds showed intermediate activity on 2 fungi strains. The in silico study showed that there were 2 targets suitable with the in vitro results.
简介：查耳酮化合物具有多种生物活性，引起了人们的极大兴趣。吗啉是药物化学中常用的杂环。它可以增强其化合物的药效、药代动力学和生物活性。研究方法在查尔酮支架中加入吗啉有助于创造具有良好生物活性的新化合物。本研究开发了一种新的平行合成程序。利用这一程序，成功合成了 18 种新型吗啉烷氧基查尔酮。通过琼脂扩散法对 5 种细菌和 2 种真菌菌株进行了抗菌和抗真菌活性评估。结果：通过琼脂稀释法测定了具有良好抑菌作用的化合物的 MIC 值。在测试的化合物中，B.21 对粪肠球菌的抑制效果最好，MIC 值为 0.6 mM。B.43 对 A. niger 和 C. albicans 的作用最好，MIC 值为 2.04 mM。结论：硅学研究发现了两个与体外研究结果一致的靶点。较长的烷基链增强了活性，同时 A 环和 B 环上都存在 OH、NH2 和卤素基团：我们合成了 18 种新的吗啉基烷氧基查耳酮，其 A 环和 B 环上都有链。3 个化合物对 5 种细菌菌株显示出中等活性，8 个化合物对 2 种真菌菌株显示出中等活性。硅学研究表明，有 2 个目标与体外结果相吻合。
{"title":"Synthesis and Evaluation of Antibacterial and Antifungal Activities In vitro and In silico of Novel Morpholinoalkoxychalcones","authors":"Hoang Minh Phan, Tan Thanh Mai, Thinh Nguyen Quang Don, Dat Thanh Do, Khac Minh Thai, Thanh Dao Tran, Phuong Truong, Phuong Nguyen Hoai Huynh","doi":"10.2174/0115734064316022240801093905","DOIUrl":"https://doi.org/10.2174/0115734064316022240801093905","url":null,"abstract":"Introduction: Chalcone compounds exhibit diverse bioactivities, attracting significant interest. Morpholine is a heterocycle commonly used in medicinal chemistry. It could enhance the potency, pharmacokinetics, and bioactivities of its compounds. Method: Adding morpholine into the chalcone scaffold could help create new compounds with favorable bioactivities. In this study, a new parallel synthesis procedure has been developed. Using this procedure, 18 novel morpholinoalkoxychalcones have been successfully synthesized. They had chains with morpholine appended on ring A or ring B. All the synthesized compounds were evaluated for the antibacterial and antifungal activities by agar diffusion method on 5 bacteria and 2 fungi strains. Results: The compounds with good inhibition were determined with respect to the MIC values by the agar dilution method. Among the tested compounds, B.21 was found to be the best against S. faecalis, with an MIC value of 0.6 mM. B.43 was found to be the best against A. niger and C. albicans with MIC value of 2.04 mM. Conclusion: The in silico study has revealed two targets to align with the in vitro results. Longer alkyl chains have enhanced the activity, along with the presence of OH, NH2, and halogen groups on both rings A and B. result: We synthesis 18 new morpholinoalkoxychalcones with the chain both on ring A and ring B. All compounds are new based on Scifinder at 10/2023. 3 compounds showed intermediate activity on 5 bacteria strains and 8 compounds showed intermediate activity on 2 fungi strains. The in silico study showed that there were 2 targets suitable with the in vitro results.","PeriodicalId":18382,"journal":{"name":"Medicinal Chemistry","volume":"13 1","pages":""},"PeriodicalIF":2.3,"publicationDate":"2024-08-12","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142219153","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2024-08-12DOI: 10.2174/0115734064326879240801043412
Isha Mishra, Vikram Sharma, Nitin Kumar, Gaurav Krishna, Vandana Arora Sethi, Ravi Mittal, Prashant K. Dhakad, Raghav Mishra
Objectives: Thiophene is one of the most important heterocyclic scaffolds with notable pharmacological properties. Thiophene and its derivatives are of particular interest among sulphurcontaining heterocycles because of their similarities to numerous natural and synthetic compounds with identified potential. The purpose of this study is to extensively analyse the synthetic pathways adopted for synthesising thiophene derivatives and investigate their various biological functions. Methods: A comprehensive review of the existing literature was conducted to collect data pertaining to the methods that are employed for the synthesis of thiophene derivatives. A comprehensive search was carried out through relevant databases, including work published in 2024. A variety of synthesis procedures were identified and arranged, encompassing both traditional approaches like the Gewald reaction and contemporary ones like microwave-assisted synthesis and green synthesis. In addition, a comprehensive compilation of in vitro and in vivo studies was conducted to investigate the biological effects of 50 distinct thiophene derivatives. The primary focus of the studies was on various activities such as anti-cancer, anti-inflammatory, antiprotozoal, antibacterial, antioxidant, and antiviral functions. Results: Diverse methodologies have been employed in the synthesis of thiophene derivatives, encompassing both conventional and modern methods. Furthermore, the biological potential of thiophene derivatives was investigated, demonstrating a broad range of actions. Key structural elements necessary for biological activity were clarified by investigations of the structure-activity relationship. Conclusion: The biological potential and flexible synthesis pathways of thiophene derivatives make them attractive candidates for use in medicinal and pharmaceutical chemistry. Understanding the different synthesis methods and biological actions of thiophene derivatives may assist rational design and create novel treatments for a variety of conditions. The potential for these compounds to be further explored and optimised is considerable for the next drug development initiatives.
{"title":"Exploring Thiophene Derivatives: Synthesis Strategies and Biological Significance","authors":"Isha Mishra, Vikram Sharma, Nitin Kumar, Gaurav Krishna, Vandana Arora Sethi, Ravi Mittal, Prashant K. Dhakad, Raghav Mishra","doi":"10.2174/0115734064326879240801043412","DOIUrl":"https://doi.org/10.2174/0115734064326879240801043412","url":null,"abstract":"Objectives: Thiophene is one of the most important heterocyclic scaffolds with notable pharmacological properties. Thiophene and its derivatives are of particular interest among sulphurcontaining heterocycles because of their similarities to numerous natural and synthetic compounds with identified potential. The purpose of this study is to extensively analyse the synthetic pathways adopted for synthesising thiophene derivatives and investigate their various biological functions. Methods: A comprehensive review of the existing literature was conducted to collect data pertaining to the methods that are employed for the synthesis of thiophene derivatives. A comprehensive search was carried out through relevant databases, including work published in 2024. A variety of synthesis procedures were identified and arranged, encompassing both traditional approaches like the Gewald reaction and contemporary ones like microwave-assisted synthesis and green synthesis. In addition, a comprehensive compilation of in vitro and in vivo studies was conducted to investigate the biological effects of 50 distinct thiophene derivatives. The primary focus of the studies was on various activities such as anti-cancer, anti-inflammatory, antiprotozoal, antibacterial, antioxidant, and antiviral functions. Results: Diverse methodologies have been employed in the synthesis of thiophene derivatives, encompassing both conventional and modern methods. Furthermore, the biological potential of thiophene derivatives was investigated, demonstrating a broad range of actions. Key structural elements necessary for biological activity were clarified by investigations of the structure-activity relationship. Conclusion: The biological potential and flexible synthesis pathways of thiophene derivatives make them attractive candidates for use in medicinal and pharmaceutical chemistry. Understanding the different synthesis methods and biological actions of thiophene derivatives may assist rational design and create novel treatments for a variety of conditions. The potential for these compounds to be further explored and optimised is considerable for the next drug development initiatives.","PeriodicalId":18382,"journal":{"name":"Medicinal Chemistry","volume":"12 1","pages":""},"PeriodicalIF":2.3,"publicationDate":"2024-08-12","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142219152","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2024-07-19DOI: 10.2174/0115734064320232240709105228
Kakali Sarkar, Sudhan Debnath, Debanjan Sen, Supratik Kar, Samir Kumar Sil
Background: Overexpression of HDAC8 was observed in various cancers and inhibition of HDAC8 has emerged as a promising therapeutic approach in recent decades.
Objective: This review aims to facilitate the discovery of novel selective HDAC8 inhibitors by analyzing the structural scaffolds of 66 known selective HDAC8 inhibitors, along with their IC50 values against HDAC8 and other HDACs.
Methods: The inhibitors were clustered based on structural symmetry, and common pharmacophores for each cluster were identified using Phase. Molecular docking with all HDACs was performed to determine binding affinity and crucial interacting residues for HDAC8 inhibition. Representative inhibitors from each cluster were subjected to molecular dynamics simulation to analyze RMSD, RMSF, active site amino acid residues, and crucial interacting residues responsible for HDAC8 inhibition. The study reviewed the active site amino acid information, active site cavities of all HDACs, and the basic structure of Zn2+ binding groups.
Results: Common pharmacophores identified included AADHR_1, AADDR_1, ADDR_1, ADHHR_1, and AADRR_1. Molecular docking analysis revealed crucial interacting residues: HIS- 142, GLY-151, HIS-143, PHE-152, PHE-20 in the main pocket, and ARG-37, TYR-100, TYR-111, TYR-306 in the secondary pocket. The RMSD of protein and RMSF of active site amino acid residues for stable protein-ligand complexes were less than 2.4 Å and 1.0 Å, respectively, as identified from MD trajectories. The range of Molecular Mechanics Generalized Born Surface Area (MMGBSA) ΔG predicted from MD trajectories was between -15.8379 Å and -61.5017 Å kcal/mol.
Conclusion: These findings may expedite the rapid discovery of selective HDAC8 inhibitors subject to experimental evaluation.
{"title":"Crucial Structural Understanding for Selective HDAC8 Inhibition: Common Pharmacophores, Molecular Docking, Molecular Dynamics, and Zinc Binder Analysis of selective HDAC8 inhibitors.","authors":"Kakali Sarkar, Sudhan Debnath, Debanjan Sen, Supratik Kar, Samir Kumar Sil","doi":"10.2174/0115734064320232240709105228","DOIUrl":"https://doi.org/10.2174/0115734064320232240709105228","url":null,"abstract":"<p><strong>Background: </strong>Overexpression of HDAC8 was observed in various cancers and inhibition of HDAC8 has emerged as a promising therapeutic approach in recent decades.</p><p><strong>Objective: </strong>This review aims to facilitate the discovery of novel selective HDAC8 inhibitors by analyzing the structural scaffolds of 66 known selective HDAC8 inhibitors, along with their IC50 values against HDAC8 and other HDACs.</p><p><strong>Methods: </strong>The inhibitors were clustered based on structural symmetry, and common pharmacophores for each cluster were identified using Phase. Molecular docking with all HDACs was performed to determine binding affinity and crucial interacting residues for HDAC8 inhibition. Representative inhibitors from each cluster were subjected to molecular dynamics simulation to analyze RMSD, RMSF, active site amino acid residues, and crucial interacting residues responsible for HDAC8 inhibition. The study reviewed the active site amino acid information, active site cavities of all HDACs, and the basic structure of Zn2+ binding groups.</p><p><strong>Results: </strong>Common pharmacophores identified included AADHR_1, AADDR_1, ADDR_1, ADHHR_1, and AADRR_1. Molecular docking analysis revealed crucial interacting residues: HIS- 142, GLY-151, HIS-143, PHE-152, PHE-20 in the main pocket, and ARG-37, TYR-100, TYR-111, TYR-306 in the secondary pocket. The RMSD of protein and RMSF of active site amino acid residues for stable protein-ligand complexes were less than 2.4 Å and 1.0 Å, respectively, as identified from MD trajectories. The range of Molecular Mechanics Generalized Born Surface Area (MMGBSA) ΔG predicted from MD trajectories was between -15.8379 Å and -61.5017 Å kcal/mol.</p><p><strong>Conclusion: </strong>These findings may expedite the rapid discovery of selective HDAC8 inhibitors subject to experimental evaluation.</p>","PeriodicalId":18382,"journal":{"name":"Medicinal Chemistry","volume":" ","pages":""},"PeriodicalIF":1.9,"publicationDate":"2024-07-19","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141748544","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
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