Article
Chemistry, Medicinal
Kurumurthy Kammari, Kiran Devaraya, Sarita Swain, Anand K. Kondapi
Summary: This study found that by adding chalcone and methyl groups to the pyridine scaffold, the desired proximity length between the pyridine scaffold and charged centers can be achieved, resulting in inhibitory activity against TopoIIbetaKHIV-1 and viral replication.
EUROPEAN JOURNAL OF MEDICINAL CHEMISTRY
(2023)
Article
Chemistry, Physical
Laise P. A. Chiari, Aldineia P. da Silva, Aline A. de Oliveira, Celio F. Lipinski, Kathia M. Honorio, Alberico B. F. da Silva
Summary: Neuropathic pain is a difficult-to-treat syndrome that significantly impacts patients' quality of life, with current drugs showing limitations. Research suggests the sigma-1 receptor as a promising target for treatment. Using QSAR techniques, new sigma-1R antagonists with significant biological affinity values were successfully designed and validated.
JOURNAL OF MOLECULAR STRUCTURE
(2021)
Article
Biochemistry & Molecular Biology
Takuya Kobayakawa, Masaru Yokoyama, Kohei Tsuji, Masayuki Fujino, Masaki Kurakami, Sayaka Boku, Miyuki Nakayama, Moemi Kaneko, Nami Ohashi, Osamu Kotani, Tsutomu Murakami, Hironori Sato, Hirokazu Tamamura
Summary: A small molecule designed to mimic hydrophobic interactions between HIV-1 capsid proteins has shown significant anti-HIV-1 activity. Structure activity relationship (SAR) studies of its derivatives provide valuable information for the design and development of novel anti-HIV agents targeting the capsid protein. This new drug has the potential to be an effective treatment for HIV in the future.
Article
Immunology
Poonam Suryawanshi, Rajani Bagul, Ashwini Shete, Madhuri Thakar
Summary: The study demonstrated that HIV-1 Env could serve as a latency reversal agent (LRA), and only ADCC mediating antibodies were able to kill the reactivated HIV reservoirs. The findings have implications in designing antibody-mediated immunotherapy for eradicating latent HIV reservoir.
FRONTIERS IN IMMUNOLOGY
(2021)
Article
Chemistry, Multidisciplinary
Takuya Kobayakawa, Masaru Yokoyama, Kohei Tsuji, Masayuki Fujino, Masaki Kurakami, Takato Onishi, Sayaka Boku, Takahiro Ishii, Yutaro Miura, Kouki Shinohara, Yuki Kishihara, Nami Ohashi, Osamu Kotani, Tsutomu Murakami, Hironori Sato, Hirokazu Tamamura
Summary: The HIV-1 capsid is crucial for viral replication and represents a potential target for antiviral drugs. A small molecule designed to mimic the interaction between CA proteins has shown significant anti-HIV-1 activity. In this study, molecules with different structures based on this small molecule were synthesized and found to have significant anti-HIV activity, with advantages over previous compounds.
Article
Multidisciplinary Sciences
Christian Gaebler, Lilian Nogueira, Elina Stoffel, Thiago Y. Oliveira, Gaelle Breton, Katrina G. Millard, Martina Turroja, Allison Butler, Victor Ramos, Michael S. Seaman, Jacqueline D. Reeves, Christos J. Petroupoulos, Irina Shimeliovich, Anna Gazumyan, Caroline S. Jiang, Nikolaus Jilg, Johannes F. Scheid, Rajesh Gandhi, Bruce D. Walker, Michael C. Sneller, Anthony Fauci, Tae-Wook Chun, Marina Caskey, Michel C. Nussenzweig
Summary: Immunotherapy with anti-HIV-1 antibodies has the potential to suppress infection and increase the rate of clearance of infected cells. A clinical study showed that 76% of HIV-infected individuals who received a combination of antibodies maintained virologic suppression for at least 20 weeks without antiretroviral therapy. The administration of antibodies affected the HIV-1 reservoir, but further research is needed to define the precise effect of antibody immunotherapy.
Article
Biochemistry & Molecular Biology
Wanting Xie, Sopon Wiriyarattanakul, Thanyada Rungrotmongkol, Liyi Shi, Amphawan Wiriyarattanakul, Phornphimon Maitarad
Summary: A series of pyrrole derivatives were studied using QSAR in order to investigate their antioxidant scavenging activities. The GA-MLR and QSAR-ANN models were used to establish relationships between the molecular descriptors and the scavenging activities. Both models showed good predictive abilities, with high R-2 values and low RMSE values in the test set. The key molecular descriptors for the antioxidant activities were bond length, HOMO energy, polarizability, and AlogP.
Article
Biochemistry & Molecular Biology
Gen Lu, Fei Pan, Xiaotong Li, Zehui Zhu, Lei Zhao, Ya Wu, Wenli Tian, Wenjun Peng, Jinling Liu
Summary: Flavonoids have been recognized for their antidiabetic effects, particularly their inhibitory effect on DPP-IV activity. However, finding novel and potent anti-DPP-IV flavonoid derivatives experimentally is challenging due to the rich variety of natural flavonoid derivatives and the significant differences in their inhibitory activities against DPP-IV caused by subtle structural differences. Therefore, a fusion strategy based on a QSAR model is proposed to streamline the discovery of flavonoid derivatives with potent anti-DPP-IV activity.
JOURNAL OF BIOMOLECULAR STRUCTURE & DYNAMICS
(2023)
Article
Immunology
An-Liang Guo, Jin-Fang Zhao, Lin Gao, Hui-Huang Huang, Ji-Yuan Zhang, Chao Zhang, Jin-Wen Song, Ruo-Nan Xu, Xing Fan, Ming Shi, Yan-Mei Jiao, Fu-Sheng Wang
Summary: The study found that CD11c(+) CD8(+) T cells can effectively control viral replication during HIV-1 infection and have the potential to be used as an immunotherapeutic approach.
FRONTIERS IN IMMUNOLOGY
(2021)
Article
Biochemistry & Molecular Biology
Anastasia L. Khandazhinskaya, Vincenzo Mercurio, Anna A. Maslova, Rogers Alberto Nahui Palomino, Mikhail S. Novikov, Elena S. Matyugina, Maria P. Paramonova, Marina K. Kukhanova, Natalya E. Fedorova, Kirill Yurlov, Alla A. Kushch, Olga Tarasova, Leonid Margolis, Sergey N. Kochetkov, Christophe Vanpouille
Summary: Efficient dual-targeted drugs against both HIV-1 and CMV have been developed, showing low cytotoxicity and effective inhibition of both viruses in cell lines. Further development of such compounds may lead to the development of dual-targeted anti-CMV/HIV-1 drugs.
Article
Chemistry, Multidisciplinary
Jurica Novak, Prateek Pathak, Maria A. Grishina, Vladimir A. Potemkin
Summary: A novel approach combining neural networks and linear regression algorithms was used to design new molecules with desired properties. Molecular descriptors based on Continual Molecular Interior analysis (CoMIn) and Cinderella's Shoe (CiS) were used to build models for cytotoxicity and anti-HIV activity. A genetic algorithm coupled with the Des-Pot Grid algorithm was used to generate new molecules from a predefined pool and predict their bioactivity and cytotoxicity. 16 hit molecules with high anti-HIV activity and low cytotoxicity were proposed, and the anti-SARS-CoV-2 activity of the hits was predicted.
JOURNAL OF COMPUTATIONAL CHEMISTRY
(2023)
Article
Automation & Control Systems
Joyce K. Dare, Matheus P. Freitas
Summary: This study explores different approaches for encoding three-dimensional information into MIA-QSAR descriptors and successfully applies them to three datasets of antiviral compounds. The models established show satisfactory performance in both internal and external validation, with correlation statistical results similar to previous studies.
CHEMOMETRICS AND INTELLIGENT LABORATORY SYSTEMS
(2021)
Review
Chemistry, Multidisciplinary
Sanjeev Kumar, Swarandeep Singh, Kalpana Luthra
Summary: In this Review, recent developments in the discovery and applications of anti-human immunodeficiency virus type- 1 (HIV-1) broadly neutralizing antibodies (bnAbs) isolated from infected adults and children were addressed. The advancements in human antibody isolation technologies have led to the discovery of highly potent anti-HIV-1 bnAbs. The characteristics of recently identified bnAbs targeted at distinct epitopes of HIV-1, as well as the existing antibodies from adults and children, were discussed, emphasizing the benefits of multispecific HIV-1 bnAbs and their role in the design of polyvalent vaccines.
Article
Biology
You-Yuan Wang, Cheng Zhen, Wei Hu, Hui-Huang Huang, Yan-Jun Li, Ming-Ju Zhou, Jing Li, Yu-Long Fu, Peng Zhang, Xiao-Yu Li, Tao Yang, Jin-Wen Song, Xing Fan, Jun Zou, Si-Run Meng, Ya-Qin Qin, Yan-Mei Jiao, Ruonan Xu, Ji-Yuan Zhang, Chun-Bao Zhou, Jin-Hong Yuan, Lei Huang, Ming Shi, Liang Cheng, Fu-Sheng Wang, Chao Zhang
Summary: Plasma glutamate levels are increased in PLWH and negatively correlate with the anti-HIV function of CD8+ T cells. Metabolic modeling shows that glutamate metabolism is robust in TVM cells. Glutamate inhibits TVM cell function via the mTORC1 pathway. There is an association between metabolic plasticity and CD8+ T cell-mediated HIV control.
COMMUNICATIONS BIOLOGY
(2023)
Article
Biochemistry & Molecular Biology
R. P. Bhole, C. G. Bonde, S. C. Bonde, R. V. Chikhale, R. D. Wavhale
Summary: A pharmacophore and 3D QSAR model for HIV Capsid Protein inhibitors was designed to predict novel inhibitors, showing promising results which can be applied to identify potential new chemical entities with better HIV-1 capsid assembly inhibition.
JOURNAL OF BIOMOLECULAR STRUCTURE & DYNAMICS
(2021)
Article
Automation & Control Systems
Joyce K. Dare, Matheus P. Freitas
Summary: This study explores different approaches for encoding three-dimensional information into MIA-QSAR descriptors and successfully applies them to three datasets of antiviral compounds. The models established show satisfactory performance in both internal and external validation, with correlation statistical results similar to previous studies.
CHEMOMETRICS AND INTELLIGENT LABORATORY SYSTEMS
(2021)
Article
Chemistry, Physical
Daniela Rodrigues Silva, Lucas de Azevedo Santos, Trevor A. Hamlin, Celia Fonseca Guerra, Matheus P. Freitas, F. Matthias Bickelhaupt
Summary: The study reveals that the gauche conformation of 1,2-dihaloethanes is favored by the interplay of hyperconjugation and Pauli repulsion. As the halogen atoms increase in size, the steric Pauli repulsion becomes strong enough to override the preference for the gauche conformation, shifting the energetic preference towards the anti conformation.
Article
Chemistry, Physical
Francisco A. Martins, Matheus P. Freitas
Summary: The study reveals that replacing two hydrogen atoms in cyclododecane with iodine atoms can affect intramolecular interactions and stability, particularly in 1,7-diiodocyclododecane. Additionally, 1,5-diiodocyclododecane exhibits strong stability due to hyperconjugative interactions within the ring. This suggests that organic halogens, such as iodine, can play a role in stereochemical control in macrocycles.
INTERNATIONAL JOURNAL OF QUANTUM CHEMISTRY
(2021)
Article
Chemistry, Organic
Francisco A. Martins, Matheus P. Freitas
Summary: The study focused on the conformational behavior and boron hybridization in beta-substituted ethylboranes, with findings showing that the B-H bond tends to overlap with the C-C bond, and that the stability of conformers in 2-aminoethylborane is influenced by the substituent X.
ASIAN JOURNAL OF ORGANIC CHEMISTRY
(2021)
Article
Environmental Sciences
Natania E. Rodrigues, Adriana C. de Faria, Ingrid Pereira, Elaine F. F. da Cunha, Matheus P. Freitas
Summary: Recent research has shown promising herbicidal activities, particularly for chlorinated derivatives, in a series of substituted N-benzoyl-N'-pyrimidin-2-yl thioureas tested against Brassica napus L. The study utilized multivariate image analysis to predict inhibition of root growth and propose effective non-chlorinated candidates. The model was found to be predictive, with an average r(pred)(2) in external validation of 0.833.
BULLETIN OF ENVIRONMENTAL CONTAMINATION AND TOXICOLOGY
(2022)
Article
Chemistry, Physical
Francisco A. Martins, Poliane Chagas, Sergio S. Thomasi, Luiz C. A. Oliveira, Renata Diniz, Matheus P. Freitas
Summary: This study investigated the conformation and stability of six-membered rings containing an endocyclic phosphorus atom and a beta-fluorine substituent. It was found that some oxidized forms exhibit surprising stability in the sterically disfavored axial orientation. Different oxidized forms of sulfur compounds show variation in electrostatic interaction with fluorine and preference for arrangement.
Article
Agriculture, Multidisciplinary
Adriana C. de Faria, Joyce K. Dare, Elaine F. F. da Cunha, Matheus P. Freitas
Summary: This study investigates the molecular level of modified sulfonylureas to determine their antifungal and herbicidal activities, and provides guidance for the design of new agrochemical candidates using molecular modeling and computational methods.
JOURNAL OF AGRICULTURAL AND FOOD CHEMISTRY
(2022)
Article
Chemistry, Multidisciplinary
Joyce K. Dare, Matheus P. Freitas
Summary: This study investigates the impact of conformational information on 3D-QSAR technique and finds that the robustness of the models is more related to the alignment aspect of the structures rather than how well their tridimensional features are described.
JOURNAL OF COMPUTATIONAL CHEMISTRY
(2022)
Article
Biochemical Research Methods
Adriana C. de Faria, Joyce K. Dare, Elaine F. F. da Cunha, Matheus P. Freitas
Summary: This study proposes unprecedented pyrimidine compounds with herbicidal activity through QSAR modeling and analysis of MIA descriptors. By investigating the quantitative structure-activity relationship of derivatives, the study reveals the structural features responsible for herbicidal activity and analyzes the interaction with the target enzyme, leading to the identification of promising herbicidal candidates.
JOURNAL OF MOLECULAR GRAPHICS & MODELLING
(2022)
Article
Agriculture, Multidisciplinary
Francisco Antonio Martins, Joyce K. Dare, Matheus P. Freitas
Summary: Aryloxyacetic acid derivatives showed promising herbicidal performance through inhibition of HPPD enzyme. By using QSAR and docking strategies, new analogues were proposed to improve herbicidal properties and minimize ecological issues.
JOURNAL OF AGRICULTURAL AND FOOD CHEMISTRY
(2022)
Article
Chemistry, Physical
Francisco A. Martins, Matheus P. Freitas
Summary: This study investigates the conformational behavior of HCHs and HFHs through quantum-chemical calculations, and explores their potential as biological compounds by docking them inside potential targets. The results suggest that HFHs could serve as alternatives to HCHs with similar ligand-protein interactions, and highlight the role of fluorine in distribution and bioaccumulation.
Article
Chemistry, Organic
Francisco A. Martins, Lucas de Azevedo Santos, Daniela Rodrigues Silva, Celia Fonseca Guerra, F. Matthias Bickelhaupt, Matheus P. Freitas
Summary: The gauche conformer in 1-X,2-Y-disubstituted ethanes is only favored for relatively small substituents, while the anti conformer is generally favored for larger substituents. In 2-iodoethanol, the gauche conformer is preferred when the hydroxyl hydrogen is oriented toward the iodine atom.
JOURNAL OF ORGANIC CHEMISTRY
(2022)
Article
Chemistry, Organic
Daniela Rodrigues Silva, Lucas A. Zeoly, Pascal Vermeeren, Rodrigo A. Cormanich, Trevor A. Hamlin, Celia Fonseca Guerra, Matheus P. Freitas
Summary: We investigated the stereoselectivity and reactivity of sodium borohydride reduction of 2-X-cyclohexanones (X=H, Cl, Br) using a combined approach of competitive experiments and density functional theory calculations. The results showed that the hydride addition proceeded via a late transition state and the reaction barrier decreased as the halogen substitution decreased, in line with relative reactivities observed in the competitive experiments. Moreover, including implicit solvation in combination with an explicit solvent molecule was crucial to accurately reproduce the experimentally observed stereoselective formation of the cis product.
JOURNAL OF PHYSICAL ORGANIC CHEMISTRY
(2023)
Article
Agriculture, Multidisciplinary
Luiz R. Capucho, Ingrid V. Pereira, Adriana C. de Faria, Joyce K. Dare, Elaine F. F. da Cunha, Matheus P. Freitas
Summary: In this study, two sets of newly synthesized mesotrione analogs were investigated using multivariate image analysis applied to quantitative structure-activity relationships (MIA-QSAR). The results showed that the MIA-QSAR models based on van der Waals radii, electronegativity, and the r(vdW)/epsilon ratio were able to accurately predict the herbicidal activities of these compounds. Docking studies also revealed promising agrochemical candidates. Overall, the combination of multivariate image analysis and docking studies can reliably predict the herbicidal activities of mesotrione analogs.
JOURNAL OF THE SCIENCE OF FOOD AND AGRICULTURE
(2023)
Article
Chemistry, Multidisciplinary
Natania E. Rodrigues, Matheus P. Freitas
Summary: This study investigates the herbicidal activity of various sulfonylurea derivatives against Brassica napus and identifies multivariate image analysis descriptors that correlate well with growth inhibition. These descriptors can be used to estimate the inhibitory concentration of unknown derivatives. Based on the analysis of substituent effects, four potential agrochemical candidates are proposed.
NEW JOURNAL OF CHEMISTRY
(2022)
