Pub Date : 2023-08-23DOI: 10.2174/2211352521666230823094517
P. Mohite, Deepali Nahar, Ankita Lonkar, A. Kadam, Kaustubh Desale
Heterocyclic compounds with a tetrazole core are of great interest because they represent an important class of synthetic compounds with a wide range of relevant biological properties that have the potential to be clinically translated as treatments for a variety of disorders. Due to their beneficial bioactivities, heterocycles with a tetrazole scaffold have aroused the interest of organic and medicinal chemists and sparked much attention in recent years. Tetrazoles are a form of nitrogen heterocycle found in several natural compounds in addition to their pharmacologically active nucleus. The tetrazole ring is similar to carboxylic acids and acts as a bioisostere analogue. A booster is a set of molecules with identical physiological features, including biological activity. Tetrazole nuclei are found in compounds used to evaluate new antimicrobial, anticancer, antitubercular, anticonvulsant, antimalarial, antihypertensive, and anti-inflammatory medicines. Tetrazole and its derivatives' broad and potent actions have established them as pharmacologically significant scaffolds. So far, tetrazole ring alterations have proven to be highly efficient, with greater efficacy. This review aims to provide an in-depth recapitulation of recent trends used to synthesize promising Tetrazole incorporated compounds and focus on the clinical significance of functionalized tetrazole analogues, which would essentially aid medicinal chemists in new research exploration and discovery in this field.
{"title":"Tetrazoles Leitmotif: An Intriguing Insight into Contemporary Developments and Biological Activities","authors":"P. Mohite, Deepali Nahar, Ankita Lonkar, A. Kadam, Kaustubh Desale","doi":"10.2174/2211352521666230823094517","DOIUrl":"https://doi.org/10.2174/2211352521666230823094517","url":null,"abstract":"\u0000\u0000Heterocyclic compounds with a tetrazole core are of great interest because they represent an important class of synthetic compounds with a wide range of relevant biological properties that have the potential to be clinically translated as treatments for a variety of disorders. Due to their beneficial bioactivities, heterocycles with a tetrazole scaffold have aroused the interest of organic and medicinal chemists and sparked much attention in recent years. Tetrazoles are a form of nitrogen heterocycle found in several natural compounds in addition to their pharmacologically active nucleus. The tetrazole ring is similar to carboxylic acids and acts as a bioisostere analogue. A booster is a set of molecules with identical physiological features, including biological activity. Tetrazole nuclei are found in compounds used to evaluate new antimicrobial, anticancer, antitubercular, anticonvulsant, antimalarial, antihypertensive, and anti-inflammatory medicines. Tetrazole and its derivatives' broad and potent actions have established them as pharmacologically significant scaffolds. So far, tetrazole ring alterations have proven to be highly efficient, with greater efficacy. This review aims to provide an in-depth recapitulation of recent trends used to synthesize promising Tetrazole incorporated compounds and focus on the clinical significance of functionalized tetrazole analogues, which would essentially aid medicinal chemists in new research exploration and discovery in this field.\u0000","PeriodicalId":7951,"journal":{"name":"Anti-Infective Agents","volume":"22 1","pages":""},"PeriodicalIF":0.0,"publicationDate":"2023-08-23","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"41292673","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2023-08-23DOI: 10.2174/2211352521666230823122601
Sangeeta Narwal, Tilak Dhanda, Prerna Sharma, Vikas Sharma, Sanchit Dhankhar, N. Garg, N. Ghosh, N. Rani
Trypanosoma cruzi, the parasite that causes Chagas disease, can only be cured with one of two drugs, benznidazole or nifurtimox. The main disadvantages of these drugs include their ineffectiveness outside of the acute or early infection phase, their unpleasant effects, and the parasite's tolerance to their activities. On the other hand, several institutions and research groups have been working on a number of ways that can help find a solution to the problem. These strategies have evolved over the last few years. Several examples of such advancements include the utilization of combination therapy, the repurposing of current treatments, and the change of dosages for traditional drugs. Research has also been conducted on antiparasitic plants and the substances that may be obtained from them, and it makes use of existing knowledge gathered through medical procedures. Some works have studied the parasite in order to identify important genes that have the potential to be used as therapeutic targets in the development of novel targeted medications. Even though a lot of these studies have shown promising results, only a small fraction of them make it to the clinical testing phase of the study. Institutions and research organizations should be rewarded for coordinating their efforts and addressing all areas of drug development, given their resources and information. Last but not least, distributing this information will result in novel Chagas disease therapies, which would assist impacted populations.
{"title":"Current Therapeutic Strategies for Chagas Disease","authors":"Sangeeta Narwal, Tilak Dhanda, Prerna Sharma, Vikas Sharma, Sanchit Dhankhar, N. Garg, N. Ghosh, N. Rani","doi":"10.2174/2211352521666230823122601","DOIUrl":"https://doi.org/10.2174/2211352521666230823122601","url":null,"abstract":"\u0000\u0000Trypanosoma cruzi, the parasite that causes Chagas disease, can only be cured with one of two drugs, benznidazole or nifurtimox. The main disadvantages of these drugs include their ineffectiveness outside of the acute or early infection phase, their unpleasant effects, and the parasite's tolerance to their activities. On the other hand, several institutions and research groups have been working on a number of ways that can help find a solution to the problem. These strategies have evolved over the last few years. Several examples of such advancements include the utilization of combination therapy, the repurposing of current treatments, and the change of dosages for traditional drugs. Research has also been conducted on antiparasitic plants and the substances that may be obtained from them, and it makes use of existing knowledge gathered through medical procedures. Some works have studied the parasite in order to identify important genes that have the potential to be used as therapeutic targets in the development of novel targeted medications. Even though a lot of these studies have shown promising results, only a small fraction of them make it to the clinical testing phase of the study. Institutions and research organizations should be rewarded for coordinating their efforts and addressing all areas of drug development, given their resources and information. Last but not least, distributing this information will result in novel Chagas disease therapies, which would assist impacted populations.\u0000","PeriodicalId":7951,"journal":{"name":"Anti-Infective Agents","volume":" ","pages":""},"PeriodicalIF":0.0,"publicationDate":"2023-08-23","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"41699506","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2023-08-22DOI: 10.2174/2211352521666230822104016
E. Benyagoub
Staphylococcus aureus is a bacterial pathogen responsible for many diseases. Multidrug resistance in S aureus has become common worldwide and is a serious clinical issue in the treatment and care of S. aureus-infected patients. S. aureus uropathogenic strains isolated from patients with UTI in Bechar province (Algeria) were phenotypically identified and evaluated for multiple drug resistance (MDR) patterns against recommended antimicrobial drugs. Through selective media, the uropathogenic S. aureus strains were isolated by analyzing a total of 211 urine samples, then subjected to various biochemical identification tests. Multidrug resistance pattern (MRSA, MLSB, and β-lactamase production) among Staphylococcus aureus uropathogenic strains was performed using phenotypic tests. A total of 50 S. aureus strains were isolated, i.e., 40,48% of all the isolated uropathogenic agents estimated at 126 isolates. More than 69% of the women had a urinary tract infection, i.e., a sex ratio (SR) of 0,43. The susceptibility test results showed that the isolated S. aureus strains were resistant to various antibiotics of the β-lactams class (penicillin, cefoxitin, and oxacillin) and were susceptible to gentamicin, chloramphenicol, co-trimoxazole, vancomycin, ofloxacin, and ciprofloxacin. Cefoxitin disk diffusion and agar screening tests showed that all the isolated S. aureus strains were qualified as MRSA at the rate of 100% (50/50), whereas a rate of 74% (37/50) was granted to MRSA using oxacillin disk diffusion test. The highest percentage of MDR-MRSA was observed in class three of antibiotics 12 (24%). The lowest percentage was observed in classes 8 and 9 of antibiotics 1 (2%). For MDR-MRSA, the MAR index ranged from 0,27 to 1,0. Penicillin disk diffusion (DD) and DDST (PI/PIT) tests showed a production rate of β-lactamase in the range of 94 and 80%, respectively. 85,1% (40/50) of penicillin-resistant strains were positive for DDST. Thus, the D-test among MRSA strains shows a rate of 38% (19/50) of cMLSB and no strain attributed to the iMLSB phenotype. This is an alarming rate, confirming the concern that is still being discussed within the medical teams of the national health sector as well as the Algerian antimicrobial resistance network, which requires prompt intervention to update a new strategy to fight antimicrobial resistance.
{"title":"Methicillin, β-lactams, and clindamycin resistance profiles of Staphylococcus aureus strains isolated from patients with UTI in Bechar province (Algeria)","authors":"E. Benyagoub","doi":"10.2174/2211352521666230822104016","DOIUrl":"https://doi.org/10.2174/2211352521666230822104016","url":null,"abstract":"\u0000\u0000Staphylococcus aureus is a bacterial pathogen responsible for many diseases. Multidrug resistance in S aureus has become common worldwide and is a serious clinical issue in the treatment and care of S. aureus-infected patients. S. aureus uropathogenic strains isolated from patients with UTI in Bechar province (Algeria) were phenotypically identified and evaluated for multiple drug resistance (MDR) patterns against recommended antimicrobial drugs.\u0000\u0000\u0000\u0000Through selective media, the uropathogenic S. aureus strains were isolated by analyzing a total of 211 urine samples, then subjected to various biochemical identification tests. Multidrug resistance pattern (MRSA, MLSB, and β-lactamase production) among Staphylococcus aureus uropathogenic strains was performed using phenotypic tests.\u0000A total of 50 S. aureus strains were isolated, i.e., 40,48% of all the isolated uropathogenic agents estimated at 126 isolates. More than 69% of the women had a urinary tract infection, i.e., a sex ratio (SR) of 0,43. The susceptibility test results showed that the isolated S. aureus strains were resistant to various antibiotics of the β-lactams class (penicillin, cefoxitin, and oxacillin) and were susceptible to gentamicin, chloramphenicol, co-trimoxazole, vancomycin, ofloxacin, and ciprofloxacin. Cefoxitin disk diffusion and agar screening tests showed that all the isolated S. aureus strains were qualified as MRSA at the rate of 100% (50/50), whereas a rate of 74% (37/50) was granted to MRSA using oxacillin disk diffusion test. The highest percentage of MDR-MRSA was observed in class three of antibiotics 12 (24%). The lowest percentage was observed in classes 8 and 9 of antibiotics 1 (2%). For MDR-MRSA, the MAR index ranged from 0,27 to 1,0.\u0000\u0000\u0000\u0000Penicillin disk diffusion (DD) and DDST (PI/PIT) tests showed a production rate of β-lactamase in the range of 94 and 80%, respectively. 85,1% (40/50) of penicillin-resistant strains were positive for DDST. Thus, the D-test among MRSA strains shows a rate of 38% (19/50) of cMLSB and no strain attributed to the iMLSB phenotype.\u0000\u0000\u0000\u0000This is an alarming rate, confirming the concern that is still being discussed within the medical teams of the national health sector as well as the Algerian antimicrobial resistance network, which requires prompt intervention to update a new strategy to fight antimicrobial resistance.\u0000","PeriodicalId":7951,"journal":{"name":"Anti-Infective Agents","volume":" ","pages":""},"PeriodicalIF":0.0,"publicationDate":"2023-08-22","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"48340783","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2023-08-09DOI: 10.2174/2211352521666230809144537
V. Rai, Pragati Thakran, Tushar Kanti Rajwar, Alok Sharma, K. Yadav, B. Kar, G. Ghosh, Goutam Rath
Linalool is a known anti-fungal molecule. It could be a good candidate against oropharyngeal candidiasis if its retention in deeper skin layers, specifically at body temperature, can be extended for a long duration. We aimed to develop and evaluate a linalool liposome-based mucoadhesive gel. The objective of this study is to improvise localization in oral mucosa by achieving sustained release, ensuring less volatility of linalool and less permeability into the systemic circulation through the mucosa. The liposomes were prepared by film formation and hydration method and characterized for particle size, polydispersity index, encapsulation efficiency, and morphological characteristics. The lipid carriers were dispersed into the gel matrix of carbopol 934 and HPMC. The gel was characterized and evaluated for in vitro drug release, ex vivo drug permeation through the goat mucosa and ex vivo dermal retention studies. The particle size and entrapment efficiency were 201 nm and 79.8%, respectively, with 0.300 PDI. Transmission Electron Microscopy revealed the spherical shape of the particles with a well-identified surface. The gel pH (6.8) was close to oral mucosal pH and had desired adhesiveness and rheological properties. The latter portrayed a slow linalool release (74.75% in 12 hours), low permeation (28.80% in 24 hours) through the mucosa and high retention (45%) compared to simple linalool gel, ensuring its improvised anti-microbial effectiveness against candida. A mucoadhesive liposomal gel offers a suitable medium for ensuring modified release, improved mucosal retention, and the ability to achieve the desired therapeutic effectiveness locally in mucosa for other drugs of volatile nature.
{"title":"The development and evaluation of linalool-loaded liposomal gel for oral candida infections: Characterization, skin permeation, dermal retention, and in vitro anti-microbial studies","authors":"V. Rai, Pragati Thakran, Tushar Kanti Rajwar, Alok Sharma, K. Yadav, B. Kar, G. Ghosh, Goutam Rath","doi":"10.2174/2211352521666230809144537","DOIUrl":"https://doi.org/10.2174/2211352521666230809144537","url":null,"abstract":"\u0000\u0000Linalool is a known anti-fungal molecule. It could be a good candidate against oropharyngeal candidiasis if its retention in deeper skin layers, specifically at body temperature, can be extended for a long duration.\u0000\u0000\u0000\u0000We aimed to develop and evaluate a linalool liposome-based mucoadhesive gel.\u0000\u0000\u0000\u0000The objective of this study is to improvise localization in oral mucosa by achieving sustained release, ensuring less volatility of linalool and less permeability into the systemic circulation through the mucosa.\u0000\u0000\u0000\u0000The liposomes were prepared by film formation and hydration method and characterized for particle size, polydispersity index, encapsulation efficiency, and morphological characteristics. The lipid carriers were dispersed into the gel matrix of carbopol 934 and HPMC.\u0000\u0000\u0000\u0000The gel was characterized and evaluated for in vitro drug release, ex vivo drug permeation through the goat mucosa and ex vivo dermal retention studies. The particle size and entrapment efficiency were 201 nm and 79.8%, respectively, with 0.300 PDI. Transmission Electron Microscopy revealed the spherical shape of the particles with a well-identified surface. The gel pH (6.8) was close to oral mucosal pH and had desired adhesiveness and rheological properties. The latter portrayed a slow linalool release (74.75% in 12 hours), low permeation (28.80% in 24 hours) through the mucosa and high retention (45%) compared to simple linalool gel, ensuring its improvised anti-microbial effectiveness against candida.\u0000\u0000\u0000\u0000A mucoadhesive liposomal gel offers a suitable medium for ensuring modified release, improved mucosal retention, and the ability to achieve the desired therapeutic effectiveness locally in mucosa for other drugs of volatile nature.\u0000","PeriodicalId":7951,"journal":{"name":"Anti-Infective Agents","volume":" ","pages":""},"PeriodicalIF":0.0,"publicationDate":"2023-08-09","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"44630631","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2023-07-18DOI: 10.2174/2211352521666230718094413
J. Jamalis, Fatma Mohamed A. Abid, Nurul Syahirah Salim, R. A. Wahab, Siti Ernieyanti Hashim, Murugesan Sankaranarayanan, A. R. Bhat
Human immunodeficiency virus (HIV) is the cause of acquired immunodeficiency syndrome (AIDS), an immunosuppressive, life-threatening condition that frequently results in other potentially fatal opportunistic infections in affected patients. Despite advancements in anti-retroviral therapy, AIDS remains the main reason for worldwide mortality. Although various anti-HIV drugs have profoundly enhanced the quality of life for AIDS patients, some patients develop resistance to the drugs, and the long-term anti-HIV treatments, and their adverse effects, prevail as major therapeutic failure causes. Therefore, concerted efforts by the scientific community are crucial to identifying new candidates for anti-HIV therapies. In this respect, the thiazolidinone moiety has acquired prominence in drug discovery and development due to its antifungal, antiviral, antidepressant, anticancer, and antibacterial properties. This moiety also demonstrated significant anti-HIV activity as a core heterocycle or derivative of substituted heterocycles. To expedite the synthesis of more novel anti-HIV drugs containing a thiazolidinone nucleus, we compiled a list of thiazolidinone-containing previously documented anti-HIV compounds. We hope that this could serve as a guide for future researchers in their design of effective thiazolidine-containing compounds showing anti-HIV activity.
{"title":"An overview of the anti-HIV potential of thiazolidinone derivatives","authors":"J. Jamalis, Fatma Mohamed A. Abid, Nurul Syahirah Salim, R. A. Wahab, Siti Ernieyanti Hashim, Murugesan Sankaranarayanan, A. R. Bhat","doi":"10.2174/2211352521666230718094413","DOIUrl":"https://doi.org/10.2174/2211352521666230718094413","url":null,"abstract":"\u0000\u0000Human immunodeficiency virus (HIV) is the cause of acquired immunodeficiency syndrome (AIDS), an immunosuppressive, life-threatening condition that frequently results in other potentially fatal opportunistic infections in affected patients. Despite advancements in anti-retroviral therapy, AIDS remains the main reason for worldwide mortality. Although various anti-HIV drugs have profoundly enhanced the quality of life for AIDS patients, some patients develop resistance to the drugs, and the long-term anti-HIV treatments, and their adverse effects, prevail as major therapeutic failure causes. Therefore, concerted efforts by the scientific community are crucial to identifying new candidates for anti-HIV therapies. In this respect, the thiazolidinone moiety has acquired prominence in drug discovery and development due to its antifungal, antiviral, antidepressant, anticancer, and antibacterial properties. This moiety also demonstrated significant anti-HIV activity as a core heterocycle or derivative of substituted heterocycles. To expedite the synthesis of more novel anti-HIV drugs containing a thiazolidinone nucleus, we compiled a list of thiazolidinone-containing previously documented anti-HIV compounds. We hope that this could serve as a guide for future researchers in their design of effective thiazolidine-containing compounds showing anti-HIV activity.\u0000","PeriodicalId":7951,"journal":{"name":"Anti-Infective Agents","volume":" ","pages":""},"PeriodicalIF":0.0,"publicationDate":"2023-07-18","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"43991304","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2023-07-17DOI: 10.2174/2211352521666230717115823
Nathalie Moussa, Hoda Mando
Since the outbreak of the COVID-19 pandemic in 2019, the world has been racing to develop effective drugs for treating this deadly disease. Although there are now some vaccines that have somewhat alleviated global panic, the lack of approved drugs remains a persistent challenge. Consequently, there is a pressing need to discover new therapeutic molecules. In this study, we explore the application of a quantitative structure−activity relationship (QSAR) model to predict the efficacy of 28 cyclic sulfonamide derivatives against SARS-CoV-2. The model was developed using multiple linear regression, and six molecular descriptors were identified as the most significant factors in determining the inhibitory activity. This proposed QSAR model holds the potential for aiding the virtual screening and drug design process in the development of new and more effective SARS-CoV-2 inhibitors. The model was also applied to seven natural products primary sulfonamides and sulfamates, demonstrating promising activity The study results indicated that the atom count, as represented by the descriptor nCl, had the most significant impact on the inhibitory activity against SARS-CoV-2. The proposed model was validated using various statistical parameters, confirming its validity, robustness, and predictiveness, with a high correlation coefficient (R2) of 0.77 for the training group and 0.95 for the test group. Furthermore, we predicted the activity of seven natural compounds, and among them, Dealanylascamycin exhibited the highest predicted activity. Subsequently, Dealanylascamycin was docked to SARS-CoV-2 and the results of the docking study further strengthened its potential as a promising candidate against COVID-19, suggesting that it should be considered for further optimization and validation. Our findings demonstrate promising predicted inhibitory activity against SARS-CoV-2 for seven natural products, primary sulfonamides, and primary sulfamates.
{"title":"Novel and Predictive QSAR Model and Molecular Docking: New Natural Sulfonamides of Potential Concern Against SARS-Cov-2","authors":"Nathalie Moussa, Hoda Mando","doi":"10.2174/2211352521666230717115823","DOIUrl":"https://doi.org/10.2174/2211352521666230717115823","url":null,"abstract":"\u0000\u0000Since the outbreak of the COVID-19 pandemic in 2019, the world has been racing to develop effective drugs for treating this deadly disease. Although there are now some vaccines that have somewhat alleviated global panic, the lack of approved drugs remains a persistent challenge. Consequently, there is a pressing need to discover new therapeutic molecules.\u0000\u0000\u0000\u0000In this study, we explore the application of a quantitative structure−activity relationship (QSAR) model to predict the efficacy of 28 cyclic sulfonamide derivatives against SARS-CoV-2. The model was developed using multiple linear regression, and six molecular descriptors were identified as the most significant factors in determining the inhibitory activity. This proposed QSAR model holds the potential for aiding the virtual screening and drug design process in the development of new and more effective SARS-CoV-2 inhibitors. The model was also applied to seven natural products primary sulfonamides and sulfamates, demonstrating promising activity\u0000\u0000\u0000\u0000The study results indicated that the atom count, as represented by the descriptor nCl, had the most significant impact on the inhibitory activity against SARS-CoV-2. The proposed model was validated using various statistical parameters, confirming its validity, robustness, and predictiveness, with a high correlation coefficient (R2) of 0.77 for the training group and 0.95 for the test group. Furthermore, we predicted the activity of seven natural compounds, and among them, Dealanylascamycin exhibited the highest predicted activity. Subsequently, Dealanylascamycin was docked to SARS-CoV-2 and the results of the docking study further strengthened its potential as a promising candidate against COVID-19, suggesting that it should be considered for further optimization and validation.\u0000\u0000\u0000\u0000Our findings demonstrate promising predicted inhibitory activity against SARS-CoV-2 for seven natural products, primary sulfonamides, and primary sulfamates.\u0000","PeriodicalId":7951,"journal":{"name":"Anti-Infective Agents","volume":" ","pages":""},"PeriodicalIF":0.0,"publicationDate":"2023-07-17","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"45645153","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2023-07-17DOI: 10.2174/2211352521666230717111247
Dhanashri Mali, S. Amrutkar
Herpes simplex Virus type 1 (HSV-1) is a contagious human pathogen causing severe infection. In recent decades, the virus has become dormant and resistant to available treatment creating the need for the development of new therapeutic agents against it. Benzotriazole is a versatile molecule with a wide range of activities like antibacterial, antiprotozoal, antiulcer, anthelmintic, and antiproliferative activity. A series of 2-(1H- benzotriazole-1-yl) N- substituted acetohydrazide derivatives were synthesized using the method given in the literature. The derivatives were obtained in good yield and characterized by spectral methods of analysis. The antiviral activity against the glycoprotein B of Herpes Simplex Virus-I (HSV-I) was determined using molecular docking (2GUM). All compounds had strong binding affinity over the standard Acyclovir. Compound 5h had the highest binding affinity and the highest inhibitory activity. The Benzotriazole-N- substituted acetohydrazide derivatives has the highest binding affinity and good inhibition of glycoprotein B of Herpes Simplex Virus-I (HSV-I), which makes it a good antiviral agent.
1型单纯疱疹病毒(HSV-1)是一种引起严重感染的传染性人类病原体。近几十年来，这种病毒处于休眠状态，对现有的治疗方法产生了抗药性，因此需要开发新的治疗药物。苯并三唑是一种多功能分子，具有广泛的抗菌、抗原虫、抗溃疡、驱虫药和抗增殖活性。采用文献中给出的方法合成了一系列2-(1H-苯并三唑-1-酰基)N-取代的乙酰肼衍生物。所得衍生物收率高，并通过光谱分析方法进行了表征。采用分子对接法(2GUM)测定了其对单纯疱疹病毒(HSV-I)糖蛋白B的抗病毒活性。所有化合物对标准的阿昔洛韦具有很强的结合亲和力。化合物5h具有最高的结合亲和力和抑制活性。苯并三唑- n -取代乙酰肼衍生物结合亲和力最高，对单纯疱疹病毒(HSV-I)糖蛋白B具有良好的抑制作用，是一种良好的抗病毒药物。
{"title":"Virtual Screening, ADMET Analysis, and Synthesis of 2-(1H- benzotriazol-1-yl) N- substituted Acetohydrazide that binds to the Glycoprotein B of Herpes Simplex Virus-I (HSV-I)","authors":"Dhanashri Mali, S. Amrutkar","doi":"10.2174/2211352521666230717111247","DOIUrl":"https://doi.org/10.2174/2211352521666230717111247","url":null,"abstract":"\u0000\u0000Herpes simplex Virus type 1 (HSV-1) is a contagious human pathogen causing severe infection. In recent decades, the virus has become dormant and resistant to available treatment creating the need for the development of new therapeutic agents against it. Benzotriazole is a versatile molecule with a wide range of activities like antibacterial, antiprotozoal, antiulcer, anthelmintic, and antiproliferative activity.\u0000\u0000\u0000\u0000A series of 2-(1H- benzotriazole-1-yl) N- substituted acetohydrazide derivatives were synthesized using the method given in the literature. The derivatives were obtained in good yield and characterized by spectral methods of analysis. The antiviral activity against the glycoprotein B of Herpes Simplex Virus-I (HSV-I) was determined using molecular docking (2GUM).\u0000\u0000\u0000\u0000All compounds had strong binding affinity over the standard Acyclovir. Compound 5h had the highest binding affinity and the highest inhibitory activity.\u0000\u0000\u0000\u0000The Benzotriazole-N- substituted acetohydrazide derivatives has the highest binding affinity and good inhibition of glycoprotein B of Herpes Simplex Virus-I (HSV-I), which makes it a good antiviral agent.\u0000","PeriodicalId":7951,"journal":{"name":"Anti-Infective Agents","volume":" ","pages":""},"PeriodicalIF":0.0,"publicationDate":"2023-07-17","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"47998501","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2023-07-17DOI: 10.2174/2211352521666230717164854
R. Malviya, Ashutosh Kumar Singh, Rishav Sharma
Antibiotic-resistant illnesses are on the rise worldwide, and the pipeline for developing new antibiotics is drying up. As a result, researchers need to create novel compounds with antimicrobial action. Recent decades have seen a dearth of novel antibiotics because of the reliance on conventional empirical screening procedures using both natural and synthetic chemicals to find them. There is hope that the massive amount of bacterial genome sequence data that has become accessible since the sequencing of the first bacterial genome more than 20 years ago might help lead to the development of new antibiotic drugs. Genes with significant levels of conservation both within and between bacterial species can be found using comparative genomic techniques; these genes may be involved in essential bacterial functions. Bioactive chemicals found in natural products have been successfully used in treating everything from infectious diseases to cancer, but over the past 20-30 years, the effectiveness of screening methods based on fermentation has decreased. Researchers urgently need answers to the unmet demand for bacterial infection resistance. Now more than ever, with the advent of cheap, high-throughput genomic sequencing technology, natural product discovery can be revitalized. Using bioinformatics, investigators may foretell whether or not a certain microbial strain would generate compounds with novel chemical structures, which may have novel modes of action in inhibiting bacterial growth. This manuscript describes how this potential might be utilised, with a particular emphasis on manipulating the expression of dormant biosynthetic gene clusters that are hypothesised to encode new antibiotics. Additionally, it consolidates the work of the past and the present to utilise bacterial genomic data in the identification and development of new antibiotics.
{"title":"Prospects for New Antibiotics Discovered Through Genome Analysis","authors":"R. Malviya, Ashutosh Kumar Singh, Rishav Sharma","doi":"10.2174/2211352521666230717164854","DOIUrl":"https://doi.org/10.2174/2211352521666230717164854","url":null,"abstract":"\u0000\u0000Antibiotic-resistant illnesses are on the rise worldwide, and the pipeline for developing new antibiotics is drying up. As a result, researchers need to create novel compounds with antimicrobial action. Recent decades have seen a dearth of novel antibiotics because of the reliance on conventional empirical screening procedures using both natural and synthetic chemicals to find them. There is hope that the massive amount of bacterial genome sequence data that has become accessible since the sequencing of the first bacterial genome more than 20 years ago might help lead to the development of new antibiotic drugs. Genes with significant levels of conservation both within and between bacterial species can be found using comparative genomic techniques; these genes may be involved in essential bacterial functions. Bioactive chemicals found in natural products have been successfully used in treating everything from infectious diseases to cancer, but over the past 20-30 years, the effectiveness of screening methods based on fermentation has decreased. Researchers urgently need answers to the unmet demand for bacterial infection resistance. Now more than ever, with the advent of cheap, high-throughput genomic sequencing technology, natural product discovery can be revitalized. Using bioinformatics, investigators may foretell whether or not a certain microbial strain would generate compounds with novel chemical structures, which may have novel modes of action in inhibiting bacterial growth. This manuscript describes how this potential might be utilised, with a particular emphasis on manipulating the expression of dormant biosynthetic gene clusters that are hypothesised to encode new antibiotics. Additionally, it consolidates the work of the past and the present to utilise bacterial genomic data in the identification and development of new antibiotics.\u0000","PeriodicalId":7951,"journal":{"name":"Anti-Infective Agents","volume":" ","pages":""},"PeriodicalIF":0.0,"publicationDate":"2023-07-17","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"44153346","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2023-07-14DOI: 10.2174/2211352521666230714160740
E. Mehraeen, Ehsan Ghavimehr, A. Zand, Seyedahmad Seyedalinaghi, A. Karimi, Hamid Zaferani Arani, P. Mirzapour, Z. Pashaei, O. Dadras
There is a need for better treatment options against COVID-19. This systematic review aimed to assess the safety and efficacy of imatinib and nilotinib, two tyrosine kinase inhibitors (TKIs), as well as artesunate (an anti-malarial agent), whose multilayer activities against SARS, MERS, and SARS-CoV-2 pathogenesis have been suggested in laboratory and observational studies. A comprehensive search strategy targeting relevant literature on PubMed, Scopus, and Web of Science online databases was constructed. The retrieved records were reviewed and screened by title/abstract and full text with eligibility criteria, and the most pertinent articles were included in the final qualitative synthesis. This review adhered to Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) to ensure the reliability of the results. This systematic review assessed the safety and applicability of imatinib, nilotinib, and artesunate in COVID-19 patients. The results showed not only possible anti-COVID-19 effects but also acceptable safety for both generic users with comorbidities with COVID-19 and off-label use in other COVID-19 patients. Promising results were also reported enhancing the survival of COVID-19 patients. A double-blinded multicenter randomized controlled trial found survival benefits for imatinib with no significant treatment-related adverse events. However, no clinical trials or large observational studies exist for artesunate and nilotinib, and the evidence relies only on case reports and case series. Molecular mechanisms revealed in preclinical studies support the possible benefits of these medications in COVID-19 treatment. However, the scarcity of reliable evidence requires further studies on possible COVID-19 treatments, including but not limited to artesunate, nilotinib, and imatinib. Nevertheless, these drugs' lack of serious adverse events suggests their safe use for other indications during the COVID-19 pandemic.
需要针对新冠肺炎提供更好的治疗方案。这篇系统综述旨在评估伊马替尼和尼洛替尼这两种酪氨酸激酶抑制剂（TKIs）以及青蒿琥酯（一种抗疟疾药物）的安全性和有效性，实验室和观察性研究表明，它们对SARS、MERS和严重急性呼吸系统综合征冠状病毒2型发病机制具有多层活性。针对PubMed、Scopus和Web of Science在线数据库上的相关文献，构建了一个全面的搜索策略。检索到的记录按照标题/摘要和符合资格标准的全文进行了审查和筛选，最相关的文章被纳入最终的定性综合。本次评审遵循系统评审和荟萃分析（PRISMA）的首选报告项目，以确保结果的可靠性。这项系统综述评估了伊马替尼、尼洛替尼和青琥酯在新冠肺炎患者中的安全性和适用性。结果显示，对于患有新冠肺炎合并症的非专利使用者和其他新冠肺炎患者的非标签使用，不仅可能具有抗新冠肺炎的效果，而且安全性也可接受。据报道，有希望的结果也提高了新冠肺炎患者的存活率。一项双盲多中心随机对照试验发现伊马替尼的生存益处没有显著的治疗相关不良事件。然而，青蒿琥酯和尼洛替尼没有临床试验或大型观察性研究，证据仅依赖于病例报告和病例系列。临床前研究揭示的分子机制支持这些药物在新冠肺炎治疗中的可能益处。然而，由于缺乏可靠的证据，需要对可能的新冠肺炎治疗方法进行进一步研究，包括但不限于青琥酯、尼洛替尼和伊马替尼。然而 这些药物没有严重不良事件，这表明它们在新冠肺炎大流行期间可安全用于其他适应症。
{"title":"Safety and efficacy of Imatinib, Nilotinib, and Artesunate in COVID-19 patients: a systematic review of current evidence","authors":"E. Mehraeen, Ehsan Ghavimehr, A. Zand, Seyedahmad Seyedalinaghi, A. Karimi, Hamid Zaferani Arani, P. Mirzapour, Z. Pashaei, O. Dadras","doi":"10.2174/2211352521666230714160740","DOIUrl":"https://doi.org/10.2174/2211352521666230714160740","url":null,"abstract":"\u0000\u0000There is a need for better treatment options against COVID-19. This systematic review aimed to assess the safety and efficacy of imatinib and nilotinib, two tyrosine kinase inhibitors (TKIs), as well as artesunate (an anti-malarial agent), whose multilayer activities against SARS, MERS, and SARS-CoV-2 pathogenesis have been suggested in laboratory and observational studies.\u0000\u0000\u0000\u0000A comprehensive search strategy targeting relevant literature on PubMed, Scopus, and Web of Science online databases was constructed. The retrieved records were reviewed and screened by title/abstract and full text with eligibility criteria, and the most pertinent articles were included in the final qualitative synthesis. This review adhered to Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) to ensure the reliability of the results.\u0000\u0000\u0000\u0000This systematic review assessed the safety and applicability of imatinib, nilotinib, and artesunate in COVID-19 patients. The results showed not only possible anti-COVID-19 effects but also acceptable safety for both generic users with comorbidities with COVID-19 and off-label use in other COVID-19 patients. Promising results were also reported enhancing the survival of COVID-19 patients.\u0000\u0000\u0000\u0000A double-blinded multicenter randomized controlled trial found survival benefits for imatinib with no significant treatment-related adverse events. However, no clinical trials or large observational studies exist for artesunate and nilotinib, and the evidence relies only on case reports and case series. Molecular mechanisms revealed in preclinical studies support the possible benefits of these medications in COVID-19 treatment. However, the scarcity of reliable evidence requires further studies on possible COVID-19 treatments, including but not limited to artesunate, nilotinib, and imatinib. Nevertheless, these drugs' lack of serious adverse events suggests their safe use for other indications during the COVID-19 pandemic.\u0000","PeriodicalId":7951,"journal":{"name":"Anti-Infective Agents","volume":" ","pages":""},"PeriodicalIF":0.0,"publicationDate":"2023-07-14","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"44465555","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2023-07-13DOI: 10.2174/2211352521666230713162636
Mokhtar Benhanifia, Amina Soltani
Antibiotic resistance was described soon after the discovery of penicillin by Fleming. In recent years, there has been an increasing interest in developing alternatives to solve this problem. Propolis «Bee glue» has been used by humans in folk medicine since ancient times, it is a natural resinous mixture produced by honeybees (Apis mellifera) from collected parts of plants. Many studies reported that the phytochemical composition of Bee glue is complex and highly variable and depends on plant species, thus, determining their biological and pharmacological properties. Propolis is considered a potential an-ti-microbial agent that overcomes the phenomenon of antibiotic resistance. Therefore, its combination with standard antibiotics could be a very useful strategy in the medical field, to treat infectious diseases.
{"title":"Propolis, Plant Sources and Antimicrobial Activity: an overview","authors":"Mokhtar Benhanifia, Amina Soltani","doi":"10.2174/2211352521666230713162636","DOIUrl":"https://doi.org/10.2174/2211352521666230713162636","url":null,"abstract":"\u0000\u0000Antibiotic resistance was described soon after the discovery of penicillin by Fleming. In recent years, there has been an increasing interest in developing alternatives to solve this problem. \u0000Propolis «Bee glue» has been used by humans in folk medicine since ancient times, it is a natural resinous mixture produced by honeybees (Apis mellifera) from collected parts of plants. Many studies reported that the phytochemical composition of Bee glue is complex and highly variable and depends on plant species, thus, determining their biological and pharmacological properties. Propolis is considered a potential an-ti-microbial agent that overcomes the phenomenon of antibiotic resistance. Therefore, its combination with standard antibiotics could be a very useful strategy in the medical field, to treat infectious diseases.\u0000","PeriodicalId":7951,"journal":{"name":"Anti-Infective Agents","volume":" ","pages":""},"PeriodicalIF":0.0,"publicationDate":"2023-07-13","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"42833325","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
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