Sergio Serrano-Buitrago, Josué Jiménez, Ruth Prieto-Montero, Florencio Moreno, Virginia Martínez-Martínez, B. L. Maroto, Santiago de la Moya
: An example of a new BODIPY design with triplet state population is reported: BINOL-O -BODIPY-based dimer. This new design combines two easily accessible structural features with a demonstrated capability of populating triplet states without the need for iodine or heavy metals: meso - p -phenylene-bridged BODIPY dimer and BINOL-O -BODIPY.
{"title":"Exploring BINOL-O-BODIPY-Based Dimers as Advanced Chromophoric Platforms Enabling Triplet State Population","authors":"Sergio Serrano-Buitrago, Josué Jiménez, Ruth Prieto-Montero, Florencio Moreno, Virginia Martínez-Martínez, B. L. Maroto, Santiago de la Moya","doi":"10.3390/ecsoc-26-13671","DOIUrl":"https://doi.org/10.3390/ecsoc-26-13671","url":null,"abstract":": An example of a new BODIPY design with triplet state population is reported: BINOL-O -BODIPY-based dimer. This new design combines two easily accessible structural features with a demonstrated capability of populating triplet states without the need for iodine or heavy metals: meso - p -phenylene-bridged BODIPY dimer and BINOL-O -BODIPY.","PeriodicalId":255032,"journal":{"name":"The 26th International Electronic Conference on Synthetic Organic Chemistry","volume":"55 1","pages":"0"},"PeriodicalIF":0.0,"publicationDate":"2022-11-17","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"115262449","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}
Kseniya S. Frolova, A. V. Akhmerova, T. Zosim, I. Ramazanov
: An efficient catalytic system consisting of 20 mol. % FeCl 3 · 6H 2 O and 20 mol. % trifluo-romethanesulfonic acid for the amidation of binor-S in a solution of toluene with organic nitriles under the action of microwave irradiation at 100 ◦ C for 30 min was
{"title":"Microwave Activation in Fe-Catalyzed Reaction of Binor-S with Nitriles","authors":"Kseniya S. Frolova, A. V. Akhmerova, T. Zosim, I. Ramazanov","doi":"10.3390/ecsoc-26-13676","DOIUrl":"https://doi.org/10.3390/ecsoc-26-13676","url":null,"abstract":": An efficient catalytic system consisting of 20 mol. % FeCl 3 · 6H 2 O and 20 mol. % trifluo-romethanesulfonic acid for the amidation of binor-S in a solution of toluene with organic nitriles under the action of microwave irradiation at 100 ◦ C for 30 min was","PeriodicalId":255032,"journal":{"name":"The 26th International Electronic Conference on Synthetic Organic Chemistry","volume":"32 1","pages":"0"},"PeriodicalIF":0.0,"publicationDate":"2022-11-17","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"128643786","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}
: This communication reports the synthesis of a series of bis (1,4-disubstituted-1,2,3-triazoles) starting from the known (2,3,4,5) bis acetonide-protected diethyl galactarate ( 1 ). Reduction of 1 with LiAlH 4 led to dioxolane 2 (90%), which, upon treatment with CBr 4 , gave the corresponding dibromide 3 (80%). The reaction of 3 with NaN 3 in DMF afforded the key diazide 4 (95%). From the diazide 4 were obtained the bis (1,4-disubstituted-1,2,3 triazoles) 5 – 8 via click reactions with alkyl-substituted acetylenes, including triphenyltinacetylene. The physical characteristics of the new compounds, including selected values of 1 H, 13 C, and 119 Sn NMR data, are given.
{"title":"Synthesis of Bis (1,4-Disubstituted-1,2,3-triazoles) Starting from Diethyl Galactarate","authors":"V. Terraza, D. Gerbino, J. Podestá","doi":"10.3390/ecsoc-26-13689","DOIUrl":"https://doi.org/10.3390/ecsoc-26-13689","url":null,"abstract":": This communication reports the synthesis of a series of bis (1,4-disubstituted-1,2,3-triazoles) starting from the known (2,3,4,5) bis acetonide-protected diethyl galactarate ( 1 ). Reduction of 1 with LiAlH 4 led to dioxolane 2 (90%), which, upon treatment with CBr 4 , gave the corresponding dibromide 3 (80%). The reaction of 3 with NaN 3 in DMF afforded the key diazide 4 (95%). From the diazide 4 were obtained the bis (1,4-disubstituted-1,2,3 triazoles) 5 – 8 via click reactions with alkyl-substituted acetylenes, including triphenyltinacetylene. The physical characteristics of the new compounds, including selected values of 1 H, 13 C, and 119 Sn NMR data, are given.","PeriodicalId":255032,"journal":{"name":"The 26th International Electronic Conference on Synthetic Organic Chemistry","volume":"92 1","pages":"0"},"PeriodicalIF":0.0,"publicationDate":"2022-11-17","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"127845884","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}
: 1,4-Butane-sultone functionalized graphitic carbon nitride nanosheets (g-C 3 N 4 @Bu-SO 3 H) was prepared and applied as an efficient heterogeneous catalyst for the synthesis of various quina-zolines derivatives with high yield. In next step, the structure and morphology of catalyst was characterized by different analyses such as, FT-IR, EDS, XRD and FE-SEM. On the other side, considering the noticeable features of g-C 3 N 4 @Bu-SO 3 H such as high stability, easy to synthesize, non-toxicity, excellent reusability, and so on, the synthesis of 2,3-dihydroquinazolines derivatives with numerous advantages such as short reaction time reaction condition, easy separation and etc were realized.
制备了1,4-丁烷磺酸功能化石墨氮化碳纳米片(g- c3n4 @ bu - so3h)，并将其作为高效的非均相催化剂用于合成各种喹唑啉衍生物。下一步，通过FT-IR、EDS、XRD、FE-SEM等分析手段对催化剂的结构和形貌进行表征。另一方面，考虑到g- c3n4 @ bu - so3h稳定性高、易于合成、无毒、可重复使用等显著特点，实现了2,3-二氢喹唑啉衍生物的合成，具有反应时间短、反应条件好、易于分离等诸多优点。
{"title":"1,4-Butane-Sultone Functionalized Graphitic Carbon Nitride as a Highly Efficient Heterogeneous Catalyst for the Synthesis of 2,3-Dihydroquinazolines Derivatives","authors":"H. Ghafuri, Z. Nasri, Zeinab Tajik","doi":"10.3390/ecsoc-26-13672","DOIUrl":"https://doi.org/10.3390/ecsoc-26-13672","url":null,"abstract":": 1,4-Butane-sultone functionalized graphitic carbon nitride nanosheets (g-C 3 N 4 @Bu-SO 3 H) was prepared and applied as an efficient heterogeneous catalyst for the synthesis of various quina-zolines derivatives with high yield. In next step, the structure and morphology of catalyst was characterized by different analyses such as, FT-IR, EDS, XRD and FE-SEM. On the other side, considering the noticeable features of g-C 3 N 4 @Bu-SO 3 H such as high stability, easy to synthesize, non-toxicity, excellent reusability, and so on, the synthesis of 2,3-dihydroquinazolines derivatives with numerous advantages such as short reaction time reaction condition, easy separation and etc were realized.","PeriodicalId":255032,"journal":{"name":"The 26th International Electronic Conference on Synthetic Organic Chemistry","volume":"19 1","pages":"0"},"PeriodicalIF":0.0,"publicationDate":"2022-11-17","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"125270780","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}
J. Patil, Aayushi Tatiya, R. Wadekar, Tejasweeni Girase, Kiran Patel
: The blooming ethnomedicinal plant Uvaria narum (Dunal) Wall is mostly found in the deep forests of the Western Ghats and belongs to the Annonaceae family. Uvaria narum is a spreading, pubescent shrub with large, dark bluish-green leaves. Phytochemistry and pharmacognostic studies have revealed that the plant possesses a variety of phytochemicals that are remarkable and beneficial to humans. The plant also possesses a number of beneficial properties, such as antioxidant activity exhibited by the presence of polyphenols and tannins, antifungal activity brought on by the benzoic acid moiety, and tumour-fighting ability contributed by terpenoid and alkaloids. The presence of phytoconstituents in the plant has been attributed to the various medicinal properties of the plant, such as anticancer activity. The plant may also be considered for use against ageing and other diseases caused by free radicals. In vitro cytotoxicity is due to terpenoids, phytosterols, and flavonoids, whereas the liver is protected by flavonoids. The chemical profile of the plant shows that acetogenins, including stereoisomers, are important constituents of the root bark. Eczema, itching, varicose veins, haemorrhoids, jaundice, inflammation, and fever are the main ailments for which this herb is used.
{"title":"Phytochemistry of Uvaria narum: A Multifaceted Perspective and Ethnopharmacological Potential","authors":"J. Patil, Aayushi Tatiya, R. Wadekar, Tejasweeni Girase, Kiran Patel","doi":"10.3390/ecsoc-26-13670","DOIUrl":"https://doi.org/10.3390/ecsoc-26-13670","url":null,"abstract":": The blooming ethnomedicinal plant Uvaria narum (Dunal) Wall is mostly found in the deep forests of the Western Ghats and belongs to the Annonaceae family. Uvaria narum is a spreading, pubescent shrub with large, dark bluish-green leaves. Phytochemistry and pharmacognostic studies have revealed that the plant possesses a variety of phytochemicals that are remarkable and beneficial to humans. The plant also possesses a number of beneficial properties, such as antioxidant activity exhibited by the presence of polyphenols and tannins, antifungal activity brought on by the benzoic acid moiety, and tumour-fighting ability contributed by terpenoid and alkaloids. The presence of phytoconstituents in the plant has been attributed to the various medicinal properties of the plant, such as anticancer activity. The plant may also be considered for use against ageing and other diseases caused by free radicals. In vitro cytotoxicity is due to terpenoids, phytosterols, and flavonoids, whereas the liver is protected by flavonoids. The chemical profile of the plant shows that acetogenins, including stereoisomers, are important constituents of the root bark. Eczema, itching, varicose veins, haemorrhoids, jaundice, inflammation, and fever are the main ailments for which this herb is used.","PeriodicalId":255032,"journal":{"name":"The 26th International Electronic Conference on Synthetic Organic Chemistry","volume":"38 1","pages":"0"},"PeriodicalIF":0.0,"publicationDate":"2022-11-17","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"127108952","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}
Viktoryia A. Zavalinich, Liliya I. Glinskaya, P. Yakovets, Y. Faletrov, V. Shkumatov
: Zn-containing proteins play essential roles in the viability and virulence of bacteria, so are considered to be possible molecular new drug targets. Based on literature data about N -acyl-o- phenylenediamine and 2-pycolylamine as warheads of drugs and molecular probes for Zn-bearing enzymes like histone deacetylases, we guessed that N -(7-nitrobenzofurazan-4-y)- o -phenylenediamine (NBD-OPD), 2-pycolyl-( N-(7-nitrobenzofurazan-4-amine)) and ciprofloxacin 2-pycolylamide (CPF-Pic2) are potential fluorescent inhibitors of such enzymes. Molecular docking was performed for estimate affinity of the compounds to a set of bacterial enzymes, and photochemical and electrochemical properties were calculated in silico using DFT.
{"title":"Potential Fluorescent Ligands for Zn-Containing Bacterial Enzymes: In Silico Evaluation, Synthesis and Optical Properties","authors":"Viktoryia A. Zavalinich, Liliya I. Glinskaya, P. Yakovets, Y. Faletrov, V. Shkumatov","doi":"10.3390/ecsoc-26-13685","DOIUrl":"https://doi.org/10.3390/ecsoc-26-13685","url":null,"abstract":": Zn-containing proteins play essential roles in the viability and virulence of bacteria, so are considered to be possible molecular new drug targets. Based on literature data about N -acyl-o- phenylenediamine and 2-pycolylamine as warheads of drugs and molecular probes for Zn-bearing enzymes like histone deacetylases, we guessed that N -(7-nitrobenzofurazan-4-y)- o -phenylenediamine (NBD-OPD), 2-pycolyl-( N-(7-nitrobenzofurazan-4-amine)) and ciprofloxacin 2-pycolylamide (CPF-Pic2) are potential fluorescent inhibitors of such enzymes. Molecular docking was performed for estimate affinity of the compounds to a set of bacterial enzymes, and photochemical and electrochemical properties were calculated in silico using DFT.","PeriodicalId":255032,"journal":{"name":"The 26th International Electronic Conference on Synthetic Organic Chemistry","volume":"54 1","pages":"0"},"PeriodicalIF":0.0,"publicationDate":"2022-11-17","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"127330236","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}
: The outbreak of SARS-CoV-2 created the biggest crisis to human health and has adversely affected economic growth worldwide. Several vaccines emerged from manufacturers to combat COVID-19. Unfortunately, no therapeutic medication has yet been approved by the FDA for the treatment of this disease. Many researchers have performed in silico studies for the identification of potential SARS-CoV-2 inhibitors from the molecules present in Indian medicinal plants and spices. In this paper, we have performed a structure-based virtual screening (VS) of 120 compounds derived from Nigella sativa (NS) against M pro , PL pro , and spike proteins of SARS-CoV-2. Strong binding interactions of M pro occurred with hits NS-40 and NS-84, whereas hits NS-72D and NS-95D showed strong binding interactions with spike proteins. Interestingly, four promising hits (i
{"title":"Carvacrol: A PLpro Inhibitor of SARS-CoV-2 Is a Natural Weapon for COVID-19","authors":"S. Debnath, B. Debnath, P. Debnath","doi":"10.3390/ecsoc-26-13679","DOIUrl":"https://doi.org/10.3390/ecsoc-26-13679","url":null,"abstract":": The outbreak of SARS-CoV-2 created the biggest crisis to human health and has adversely affected economic growth worldwide. Several vaccines emerged from manufacturers to combat COVID-19. Unfortunately, no therapeutic medication has yet been approved by the FDA for the treatment of this disease. Many researchers have performed in silico studies for the identification of potential SARS-CoV-2 inhibitors from the molecules present in Indian medicinal plants and spices. In this paper, we have performed a structure-based virtual screening (VS) of 120 compounds derived from Nigella sativa (NS) against M pro , PL pro , and spike proteins of SARS-CoV-2. Strong binding interactions of M pro occurred with hits NS-40 and NS-84, whereas hits NS-72D and NS-95D showed strong binding interactions with spike proteins. Interestingly, four promising hits (i","PeriodicalId":255032,"journal":{"name":"The 26th International Electronic Conference on Synthetic Organic Chemistry","volume":"15 1","pages":"0"},"PeriodicalIF":0.0,"publicationDate":"2022-11-17","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"126589542","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}
N. Medjahed, Z. Kibou, A. Berrichi, R. Bachir, N. Choukchou-Braham
{"title":"Nickel-Catalyzed, One-Pot Synthesis of Pyrazoles","authors":"N. Medjahed, Z. Kibou, A. Berrichi, R. Bachir, N. Choukchou-Braham","doi":"10.3390/ecsoc-26-13687","DOIUrl":"https://doi.org/10.3390/ecsoc-26-13687","url":null,"abstract":"","PeriodicalId":255032,"journal":{"name":"The 26th International Electronic Conference on Synthetic Organic Chemistry","volume":"1 1","pages":"0"},"PeriodicalIF":0.0,"publicationDate":"2022-11-17","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"124252900","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}
Diana E. Vita, M. A. Badajoz, Marcos J. Lo Fiego, G. Silbestri
: Two gold(I) complexes have been synthesized by a two-step reaction. The first reaction step was the deprotonation with butyllithium to obtain the corresponding NHC. In the second reaction step, the metal precursor was added to afford the corresponding gold complex. At this point, the complex obtained depends on the nature of the metal precursor. A monocarbene complex (sydnone-Au-tht) was obtained using [Au(tht)Cl] as the metal precursor and a biscarbene complex (sydnone-Au-imidazolium) was obtained using a gold imidazolium complex as the metal precursor instead. The 13 C-NMR resonance frequencies of the carbene carbon atom shifted to higher values from 97.3 to 135.6–139.7 ppm, mono and biscarbene, respectively.
{"title":"Synthesis of N-Heterocyclic Carbene Gold Complexes Using 2,4,6-Trimethylphenyl Sydnone as Model Substrate †","authors":"Diana E. Vita, M. A. Badajoz, Marcos J. Lo Fiego, G. Silbestri","doi":"10.3390/ecsoc-26-13674","DOIUrl":"https://doi.org/10.3390/ecsoc-26-13674","url":null,"abstract":": Two gold(I) complexes have been synthesized by a two-step reaction. The first reaction step was the deprotonation with butyllithium to obtain the corresponding NHC. In the second reaction step, the metal precursor was added to afford the corresponding gold complex. At this point, the complex obtained depends on the nature of the metal precursor. A monocarbene complex (sydnone-Au-tht) was obtained using [Au(tht)Cl] as the metal precursor and a biscarbene complex (sydnone-Au-imidazolium) was obtained using a gold imidazolium complex as the metal precursor instead. The 13 C-NMR resonance frequencies of the carbene carbon atom shifted to higher values from 97.3 to 135.6–139.7 ppm, mono and biscarbene, respectively.","PeriodicalId":255032,"journal":{"name":"The 26th International Electronic Conference on Synthetic Organic Chemistry","volume":"5 1","pages":"0"},"PeriodicalIF":0.0,"publicationDate":"2022-11-17","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"128909474","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}
: The WHO database shows that mycobacterium tuberculosis has become an epidemic worldwide due to its pathogenicity and virulence, which have magnified its infectiousness. The situation becomes grimmer with the prevalence of MDR-TB, XDR-TB, emergence of cross-resistance, ineffectiveness of novel therapeutic targets, failure of novel medications in clinical trials, currently available drugs losing their therapeutic efficacy, lack of drug discovery efforts due to poor ROI, and the existence of co-infections; i.e., HIV, TB, COVID, and HIV-TB-COVID. Following our prior studies described by Stirret et al. in 2008, Ferreras et al. in 2011, and Shyam et al. in 2021, herein we focus on exploring pyrazoline-based mycobactin analogs (non-specific mycobactin biosynthesis inhibitors) targeting the MbtA enzyme (first step of mycobactin biosynthesis) with a hope of finding a more potent analog showing a high affinity for MbtA . The design strategy involves retaining the structural features of mycobacterial siderophores. Herein, a small library (12 molecules) of mycobactin analogs were designed, keeping the necessary skeleton (diaryl-substituted pyrazoline (DAP)) intact and assessed their stability using in silico tools. In order to determine the binding modes and inhibitory profiles of the designed ligands, docking was carried out in the active pocket of MbtA (analogous with the homologous structure with PDB ID: 1MDB). The best energy conformation (lowest score) of each docked ligand was represented graphically. The ADMET profile of each molecule was analyzed. The best molecule that revealed a good ADMET profile was taken up for MD simulation study (45 ns). Results revealed that the designed compounds GV08 ( − 8.80 kcal/mol, 352.58 nM), GV09 ( − 8.61 kcal/mol, 499.91 nM), GV03 ( − 8.59 kcal/mol, 508.51 nM), and GV07 ( − 8.54 kcal/mol, 553.44 nM) had a good docking score and inhibition constant. Of these, GV08 showed a good ADME profile with all the major parameters lying in the acceptable ranges. They also showed the least toxicity with no hepatotoxicity and skin sensitization. MD simulation studies of GV08 also suggest that it was stable throughout the course of simulation. This could be justified by RMSD, RMSF, and H-bond plots. The future scope invalidates these findings through synthesis
{"title":"Designing and In Silico Evaluation of Some Non-Nucleoside MbtA Inhibitors: On Track to Tackle Tuberculosis","authors":"Gourav Rakshit, Venkatesan Jayaprakash","doi":"10.3390/ecsoc-26-13688","DOIUrl":"https://doi.org/10.3390/ecsoc-26-13688","url":null,"abstract":": The WHO database shows that mycobacterium tuberculosis has become an epidemic worldwide due to its pathogenicity and virulence, which have magnified its infectiousness. The situation becomes grimmer with the prevalence of MDR-TB, XDR-TB, emergence of cross-resistance, ineffectiveness of novel therapeutic targets, failure of novel medications in clinical trials, currently available drugs losing their therapeutic efficacy, lack of drug discovery efforts due to poor ROI, and the existence of co-infections; i.e., HIV, TB, COVID, and HIV-TB-COVID. Following our prior studies described by Stirret et al. in 2008, Ferreras et al. in 2011, and Shyam et al. in 2021, herein we focus on exploring pyrazoline-based mycobactin analogs (non-specific mycobactin biosynthesis inhibitors) targeting the MbtA enzyme (first step of mycobactin biosynthesis) with a hope of finding a more potent analog showing a high affinity for MbtA . The design strategy involves retaining the structural features of mycobacterial siderophores. Herein, a small library (12 molecules) of mycobactin analogs were designed, keeping the necessary skeleton (diaryl-substituted pyrazoline (DAP)) intact and assessed their stability using in silico tools. In order to determine the binding modes and inhibitory profiles of the designed ligands, docking was carried out in the active pocket of MbtA (analogous with the homologous structure with PDB ID: 1MDB). The best energy conformation (lowest score) of each docked ligand was represented graphically. The ADMET profile of each molecule was analyzed. The best molecule that revealed a good ADMET profile was taken up for MD simulation study (45 ns). Results revealed that the designed compounds GV08 ( − 8.80 kcal/mol, 352.58 nM), GV09 ( − 8.61 kcal/mol, 499.91 nM), GV03 ( − 8.59 kcal/mol, 508.51 nM), and GV07 ( − 8.54 kcal/mol, 553.44 nM) had a good docking score and inhibition constant. Of these, GV08 showed a good ADME profile with all the major parameters lying in the acceptable ranges. They also showed the least toxicity with no hepatotoxicity and skin sensitization. MD simulation studies of GV08 also suggest that it was stable throughout the course of simulation. This could be justified by RMSD, RMSF, and H-bond plots. The future scope invalidates these findings through synthesis","PeriodicalId":255032,"journal":{"name":"The 26th International Electronic Conference on Synthetic Organic Chemistry","volume":"3 1","pages":"0"},"PeriodicalIF":0.0,"publicationDate":"2022-11-17","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"124488781","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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