Crystal Structure, Hirshfeld Surface Analysis and Computational Studies of Two Benzo [b][1, 4] Diazepine Derivatives
- Odame, Felix, Madanhire, T, Hosten, Eric C, Lobb, Kevin A
- Authors: Odame, Felix , Madanhire, T , Hosten, Eric C , Lobb, Kevin A
- Date: 2023
- Subjects: To be catalogued
- Language: English
- Type: text , article
- Identifier: http://hdl.handle.net/10962/452689 , vital:75162 , xlink:href="https://doi.org/10.1134/S0022476623120041"
- Description: The DFT computational studies, crystal structures and Hirshfeld surface analysis of (E)-4-(2-chlorostyryl)-2,2-dimethyl-2,3-dihydro-1H-benzo[b][1,4]diazepine (1) and (E)-4-(2-(2,2-dimethyl-2,3-dihydro-1H-benzo[b][1,4]diazepin-4-yl)vinyl)phenol (2) have been presented. The compounds crystallized in the monoclinic space group P21/c with 4 molecules in their unit cells each. The experimental and computed bond lengths and bond angles deviated from each other to some extent but also showed good agreement with each other in some cases. Hirshfeld surface analysis of the compounds provided further information about the structural properties of the compounds.
- Full Text:
- Date Issued: 2023
- Authors: Odame, Felix , Madanhire, T , Hosten, Eric C , Lobb, Kevin A
- Date: 2023
- Subjects: To be catalogued
- Language: English
- Type: text , article
- Identifier: http://hdl.handle.net/10962/452689 , vital:75162 , xlink:href="https://doi.org/10.1134/S0022476623120041"
- Description: The DFT computational studies, crystal structures and Hirshfeld surface analysis of (E)-4-(2-chlorostyryl)-2,2-dimethyl-2,3-dihydro-1H-benzo[b][1,4]diazepine (1) and (E)-4-(2-(2,2-dimethyl-2,3-dihydro-1H-benzo[b][1,4]diazepin-4-yl)vinyl)phenol (2) have been presented. The compounds crystallized in the monoclinic space group P21/c with 4 molecules in their unit cells each. The experimental and computed bond lengths and bond angles deviated from each other to some extent but also showed good agreement with each other in some cases. Hirshfeld surface analysis of the compounds provided further information about the structural properties of the compounds.
- Full Text:
- Date Issued: 2023
Unveiling the reactivity of truxillic and truxinic acids (TXAs): deprotonation, anion center dot center dot center dot HO, cation center dot center dot center dot O and cation center dot center dot center dot pi interactions in TXA (0) center dot center dot center dot Y+ and TXA (0) center dot center dot center dot Z (-) complexes (Y= Li, Na, K; Z= F, Cl, Br)
- Isamura, Bienfait K, Patouossa, Issofa, Muya, Jules T, Lobb, Kevin A
- Authors: Isamura, Bienfait K , Patouossa, Issofa , Muya, Jules T , Lobb, Kevin A
- Date: 2023
- Subjects: To be catalogued
- Language: English
- Type: text , article
- Identifier: http://hdl.handle.net/10962/452827 , vital:75173 , xlink:href="https://link.springer.com/content/pdf/10.1007/s11224-022-01965-5.pdf"
- Description: Herein, we report a quantum chemistry investigation of the interaction between µ-truxinic acid, referred to as TXA0 , and Y+ (Y=Li, Na, K) and Z− (Z=F, Cl, Br) ions using M06-2X, B3LYP and 휔 B97XD functionals in conjunction with the 6–31+ +G(d,p), aug-cc-pVDZ(-X2C) and 6–311+ +G (d, p) basis sets. Our computations suggest that Y+ cations can bind to TXA0 through several combinations of cation…O and cation-π interactions, while Z− anions generally establish anion… H–O contacts. Predicted binding energies at the M06-2X/6–311+ +G(d,p) level range between−26.6 and−70.2 kcal/mol for cationic complexes and−20.4 and−62.3 kcal/mol for anionic ones. As such, TXA0 appears as an amphoteric molecule with a slight preference for electrophilic (cation... O) attacks. Furthermore, the most favourable binding site for cations allows for the formation of O…cation…O interactions where the cation is trapped between O37 and O38 atoms of TXA0 . Anions do not behave uniformly towards TXA0 : while the fuoride anion F− induces the deprotonation of TXA0 , Br− and Cl− do not. All of these structural insights are supported by topological calculations in the context of the quantum theory of atoms in molecules (QTAIM). Finally, SAPT0 analyses suggest that TXA0 …Y+ and TXA0 …Z− complexes are mainly stabilized by electrostatic and inductive efects, whose combined contributions account for more than 60 percent of the total interaction energy.
- Full Text:
- Date Issued: 2023
- Authors: Isamura, Bienfait K , Patouossa, Issofa , Muya, Jules T , Lobb, Kevin A
- Date: 2023
- Subjects: To be catalogued
- Language: English
- Type: text , article
- Identifier: http://hdl.handle.net/10962/452827 , vital:75173 , xlink:href="https://link.springer.com/content/pdf/10.1007/s11224-022-01965-5.pdf"
- Description: Herein, we report a quantum chemistry investigation of the interaction between µ-truxinic acid, referred to as TXA0 , and Y+ (Y=Li, Na, K) and Z− (Z=F, Cl, Br) ions using M06-2X, B3LYP and 휔 B97XD functionals in conjunction with the 6–31+ +G(d,p), aug-cc-pVDZ(-X2C) and 6–311+ +G (d, p) basis sets. Our computations suggest that Y+ cations can bind to TXA0 through several combinations of cation…O and cation-π interactions, while Z− anions generally establish anion… H–O contacts. Predicted binding energies at the M06-2X/6–311+ +G(d,p) level range between−26.6 and−70.2 kcal/mol for cationic complexes and−20.4 and−62.3 kcal/mol for anionic ones. As such, TXA0 appears as an amphoteric molecule with a slight preference for electrophilic (cation... O) attacks. Furthermore, the most favourable binding site for cations allows for the formation of O…cation…O interactions where the cation is trapped between O37 and O38 atoms of TXA0 . Anions do not behave uniformly towards TXA0 : while the fuoride anion F− induces the deprotonation of TXA0 , Br− and Cl− do not. All of these structural insights are supported by topological calculations in the context of the quantum theory of atoms in molecules (QTAIM). Finally, SAPT0 analyses suggest that TXA0 …Y+ and TXA0 …Z− complexes are mainly stabilized by electrostatic and inductive efects, whose combined contributions account for more than 60 percent of the total interaction energy.
- Full Text:
- Date Issued: 2023
Insights into the Dynamics and Binding of Two Polyprotein Substrate Cleavage Points in the Context of the SARS-CoV-2 Main and Papain-like Proteases
- Sanusi, Zainab K, Lobb, Kevin A
- Authors: Sanusi, Zainab K , Lobb, Kevin A
- Date: 2022
- Subjects: To be catalogued
- Language: English
- Type: text , article
- Identifier: http://hdl.handle.net/10962/452773 , vital:75169 , xlink:href="https://doi.org/10.3390/molecules27238251"
- Description: It is well known that vital enzymes in the replication process of the coronavirus are the SARS-CoV-2 PLpro and SARS-CoV-2 3CLpro, both of which are important targets in the search for anti-coronavirus agents. These two enzymes are responsible for cleavage at various polyprotein sites in the SARS-CoV-2 lifecycle. Herein, the dynamics of the polyprotein cleavage sequences for the boundary between non-structural proteins Nsp1 and Nsp2 (CS1) and between Nsp2 and Nsp3 (CS2) in complex with both the papain-like protein PLpro and the main protease 3CLpro were explored using computational methods. The post dynamics analysis reveals that CS1 and CS2 both have greater stability when complexed with PLpro. Of these two, greater stability is observed for the CS1–PLpro complex, while destabilization resulting in loss of CS2 from the PLpro active site is observed for CS2-PLpro, suggesting the rate of exchange by the papain-like protease is faster for CS2 compared to CS1. On the other hand, the 3CLpro main protease also reveals stability for CS1 suggesting that the main protease could also play a potential role in the cleavage at point CS1. However, destabilization occurs early in the simulation for the complex CLpro–CS2 suggesting a poor interaction and non-plausible protease cleavage of the polyprotein at CS2 by the main protease. These findings could be used as a guide in the development and design of potent COVID-19 antiviral inhibitors that mimic the CS1 cleavage site.
- Full Text:
- Date Issued: 2022
- Authors: Sanusi, Zainab K , Lobb, Kevin A
- Date: 2022
- Subjects: To be catalogued
- Language: English
- Type: text , article
- Identifier: http://hdl.handle.net/10962/452773 , vital:75169 , xlink:href="https://doi.org/10.3390/molecules27238251"
- Description: It is well known that vital enzymes in the replication process of the coronavirus are the SARS-CoV-2 PLpro and SARS-CoV-2 3CLpro, both of which are important targets in the search for anti-coronavirus agents. These two enzymes are responsible for cleavage at various polyprotein sites in the SARS-CoV-2 lifecycle. Herein, the dynamics of the polyprotein cleavage sequences for the boundary between non-structural proteins Nsp1 and Nsp2 (CS1) and between Nsp2 and Nsp3 (CS2) in complex with both the papain-like protein PLpro and the main protease 3CLpro were explored using computational methods. The post dynamics analysis reveals that CS1 and CS2 both have greater stability when complexed with PLpro. Of these two, greater stability is observed for the CS1–PLpro complex, while destabilization resulting in loss of CS2 from the PLpro active site is observed for CS2-PLpro, suggesting the rate of exchange by the papain-like protease is faster for CS2 compared to CS1. On the other hand, the 3CLpro main protease also reveals stability for CS1 suggesting that the main protease could also play a potential role in the cleavage at point CS1. However, destabilization occurs early in the simulation for the complex CLpro–CS2 suggesting a poor interaction and non-plausible protease cleavage of the polyprotein at CS2 by the main protease. These findings could be used as a guide in the development and design of potent COVID-19 antiviral inhibitors that mimic the CS1 cleavage site.
- Full Text:
- Date Issued: 2022
Rational design and regioselective synthesis of conformationally restricted furan-derived ligands as potential anti-malarial agents
- Mutorwa, Marius K, Nokalipa, Iviwe, Tanner, Delia C, Blatch, Gregory L, Lobb, Kevin A, Klein, Rosalyn, Kaye, Perry T
- Authors: Mutorwa, Marius K , Nokalipa, Iviwe , Tanner, Delia C , Blatch, Gregory L , Lobb, Kevin A , Klein, Rosalyn , Kaye, Perry T
- Date: 2020
- Subjects: To be catalogued
- Language: English
- Type: text , article
- Identifier: http://hdl.handle.net/10962/447170 , vital:74589 , xlink:href="https://doi.org/10.24820/ark.5550190.p011.281"
- Description: Substituted 3-furanomethyl phosphate esters and their corresponding phosphoric acids have been prepared as conformationally restricted analogues of DOXP, the natural substrate for Plasmodium falciparum 1-deoxyD-xylulose-5-phosphate reductoisomerase (PfDXR), and fosmidomycin, an established inhibitor. Saturation Transfer Difference (STD) NMR analysis and in silico docking data suggest the potential of such compounds as PfDXR inhibitors.
- Full Text:
- Date Issued: 2020
- Authors: Mutorwa, Marius K , Nokalipa, Iviwe , Tanner, Delia C , Blatch, Gregory L , Lobb, Kevin A , Klein, Rosalyn , Kaye, Perry T
- Date: 2020
- Subjects: To be catalogued
- Language: English
- Type: text , article
- Identifier: http://hdl.handle.net/10962/447170 , vital:74589 , xlink:href="https://doi.org/10.24820/ark.5550190.p011.281"
- Description: Substituted 3-furanomethyl phosphate esters and their corresponding phosphoric acids have been prepared as conformationally restricted analogues of DOXP, the natural substrate for Plasmodium falciparum 1-deoxyD-xylulose-5-phosphate reductoisomerase (PfDXR), and fosmidomycin, an established inhibitor. Saturation Transfer Difference (STD) NMR analysis and in silico docking data suggest the potential of such compounds as PfDXR inhibitors.
- Full Text:
- Date Issued: 2020
Seed extract of Psoralea corylifolia and its constituent bakuchiol impairs AHL-based quorum sensing and biofilm formation in food-and human-related pathogens
- Husain, Fohad M, Ahmad, Iqbal, Khan, Faez I, Al-Shabib, Nasser A, Baig, Mohammad H, Hussain, Afzal, Rehman, Md T, Alajmi, Mohamed F, Lobb, Kevin A
- Authors: Husain, Fohad M , Ahmad, Iqbal , Khan, Faez I , Al-Shabib, Nasser A , Baig, Mohammad H , Hussain, Afzal , Rehman, Md T , Alajmi, Mohamed F , Lobb, Kevin A
- Date: 2018
- Subjects: To be catalogued
- Language: English
- Type: text , article
- Identifier: http://hdl.handle.net/10962/447182 , vital:74590 , xlink:href="https://doi.org/10.3389/fcimb.2018.00351"
- Description: The emergence of multi-drug resistance in pathogenic bacteria in clinical settings as well as food-borne infections has become a serious health concern. The problem of drug resistance necessitates the need for alternative novel therapeutic strategies to combat this menace. One such approach is targeting the quorum-sensing (QS) controlled virulence and biofilm formation. In this study, we first screened different fractions of Psoralea corylifolia (seed) for their anti-QS property in the Chromobacterium violaceum 12472 strain.
- Full Text:
- Date Issued: 2018
- Authors: Husain, Fohad M , Ahmad, Iqbal , Khan, Faez I , Al-Shabib, Nasser A , Baig, Mohammad H , Hussain, Afzal , Rehman, Md T , Alajmi, Mohamed F , Lobb, Kevin A
- Date: 2018
- Subjects: To be catalogued
- Language: English
- Type: text , article
- Identifier: http://hdl.handle.net/10962/447182 , vital:74590 , xlink:href="https://doi.org/10.3389/fcimb.2018.00351"
- Description: The emergence of multi-drug resistance in pathogenic bacteria in clinical settings as well as food-borne infections has become a serious health concern. The problem of drug resistance necessitates the need for alternative novel therapeutic strategies to combat this menace. One such approach is targeting the quorum-sensing (QS) controlled virulence and biofilm formation. In this study, we first screened different fractions of Psoralea corylifolia (seed) for their anti-QS property in the Chromobacterium violaceum 12472 strain.
- Full Text:
- Date Issued: 2018
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