Review
Biochemistry & Molecular Biology
Anna Egorova, Elena G. Salina, Vadim Makarov
Summary: Current guidelines for managing latent tuberculosis infection (LTBI) only include three older drugs, which have little impact on eliminating latent TB. New specific therapeutics are urgently needed to address this challenge.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2021)
Review
Microbiology
Xinyue Xu, Baoyu Dong, Lijun Peng, Chao Gao, Zhiqun He, Chuan Wang, Jumei Zeng
Summary: The dynamic cell envelope of Mycobacterium tuberculosis regulates the immune response and is a crucial target for drug and vaccine development.
FRONTIERS IN MICROBIOLOGY
(2022)
Article
Biochemistry & Molecular Biology
Ali A. Rabaan, Mohammed Garout, Mohammed Aljeldah, Basim R. Al Shammari, Abdulsalam Alawfi, Amer Alshengeti, Mustafa A. Najim, Mohammed Alrouji, Yasir Almuhanna, Mohammed Alissa, Mutaib M. Mashraqi, Ameen S. S. Alwashmi, Mashael Alhajri, Souad Mohammed Alateah, Ramadan Abdelmoez Farahat, Ranjan K. Mohapatra
Summary: This study used a computational drug design pipeline to screen potential compounds from the NP-lib database for their inhibitory effect on the RpfB protein of Mycobacterium tuberculosis. Molecular dynamics simulation and principal component analysis confirmed the effectiveness of the top 5 hits, with three compounds showing significant binding to the functional site of the RpfB protein. The results suggest promising potential for these compounds as anti-tuberculosis drugs, but further experimental validation is needed.
MOLECULAR DIVERSITY
(2023)
Review
Biochemistry & Molecular Biology
Hagyu Kim, Sung Jae Shin
Summary: Lipid species have a crucial role in the growth and virulence expression of Mycobacterium tuberculosis. Alterations in lipid metabolites of both host and Mtb influence the efficacy of anti-TB drugs and contribute to drug tolerance. This review explores the relationship between lipids and drug efficacy in various Mtb infection models and suggests novel approaches to enhance drug effectiveness.
CELLULAR AND MOLECULAR LIFE SCIENCES
(2023)
Review
Chemistry, Medicinal
Caue Benito Scarim, Renan Lira de Farias, Adelino Vieira de Godoy Netto, Chung Man Chin, Jean Leandro dos Santos, Fernando Rogerio Pavan
Summary: Metal-based drugs serve as key pharmacophores in the development of new anti-TB drugs, with promising ligands like heterocyclic compounds, phosphines, schiff bases, thio and semicarbazones, aliphatic amines, cyclopalladated, cyanometallates. Metal-based complexes show potential for treating various diseases, including infectious diseases.
EUROPEAN JOURNAL OF MEDICINAL CHEMISTRY
(2021)
Article
Microbiology
Catherine Shelton, Matthew McNeil, Renee Allen, Lindsay Flint, Dara Russell, Bryan Berube, Aaron Korkegian, Yulia Ovechkina, Tanya Parish
Summary: By studying the mutations in specific genes of Mycobacterium tuberculosis, we found that triazolopyrimidines can interact with these genes and confer resistance to the bacteria. These compounds deplete intracellular ATP levels and exhibit activity against intracellular bacteria, but have no effect on human mitochondrial respiration.
ANTIMICROBIAL AGENTS AND CHEMOTHERAPY
(2022)
Article
Chemistry, Medicinal
Leonardo Aquino Linhares, Aline dos Santos Peixoto, Luanna de Angelis Correia de Sousa, Joao Paulo Lucena Laet, Aline Caroline da Silva Santos, Valeria Rego Alves Pereira, Maria Madileuza Carneiro Neves, Luiz Felipe Gomes Rebello Ferreira, Marcelo Zaldini Hernandes, Jennifer de la Vega, Antonio Pereira-Neves, Arturo San Feliciano, Esther Del Olmo, Haiana Charifker Schindler, Lilian Maria Lapa Montenegro
Summary: Tuberculosis remains a major public health problem and the increase in multidrug-resistant variants makes it more difficult to treat and control. This study evaluated new compounds related to dihydrosphingosine and ethambutol against sensitive and pre-XDR Mycobacterium strains and characterized their pharmacological activity. Among the compounds analyzed, 11 showed good to moderate activity against sensitive and MDR Mycobacterium tuberculosis, with potential as a prototype substance for further optimization in preclinical studies.
EUROPEAN JOURNAL OF MEDICINAL CHEMISTRY
(2023)
Article
Biochemistry & Molecular Biology
Sandipan Chakraborty, Jyotirmoy Rakshit, Jaya Bandyopadhyay, Soumalee Basu
Summary: Through multiple approaches, neohesperidin is found to inhibit both BACE1 and Aβ aggregation, presenting as a potential non-toxic multi-potent scaffold for the development of Alzheimer's disease therapeutics.
INTERNATIONAL JOURNAL OF BIOLOGICAL MACROMOLECULES
(2021)
Article
Chemistry, Medicinal
Joanna C. Evans, Dinakaran Murugesan, John M. Post, Vitor Mendes, Zhe Wang, Navid Nahiyaan, Sasha L. Lynch, Stephen Thompson, Simon R. Green, Peter C. Ray, Jeannine Hess, Christina Spry, Anthony G. Coyne, Chris Abell, Helena I. M. Boshoff, Paul G. Wyatt, Kyu Y. Rhee, Tom L. Blundell, Clifton E. I. I. I. I. I. I. Barry, Valerie Mizrahi
Summary: Coenzyme A (CoA) is an essential cofactor in all living cells, and the pathway to CoA biosynthesis is considered a potential source of novel tuberculosis drug targets. This study identified a small molecule inhibitor, compound 1f, that displays on-target activity against Mtb CoaBC, confirming the druggability of this target. Metabolomic profiling following exposure to compound 1f in wild-type Mtb H37Rv produced a signature consistent with perturbations in pantothenate and CoA biosynthesis.
ACS INFECTIOUS DISEASES
(2021)
Article
Pharmacology & Pharmacy
Hongjuan Zhang, Ying Chen, Yu Zhang, Luyao Qiao, Xiangyin Chi, Yanxing Han, Yuan Lin, Shuyi Si, Jiandong Jiang
Summary: Tuberculosis is a deadly disease caused by Mycobacterium tuberculosis, and finding new drugs to combat it is urgently needed. The FtsZ/SepF interaction has been identified as a promising target for anti-TB drugs, and a compound named T0349 has been discovered to inhibit this interaction and prevent bacterial cell division.
ACTA PHARMACEUTICA SINICA B
(2023)
Article
Biochemistry & Molecular Biology
Annabel Itterbeek, Amber Possemiers, Yunus Colak, Leonard E. Backer, Abram Aertsen, Rob Lavigne, Jan Paeshuyse
Summary: This study screened Mycophage endolysins and identified CBDs with affinity to Mycobacterium bovis. The secondary structure analysis revealed the presence of potential new CBDs in other endolysins. Fusion proteins containing these CBDs were constructed and shown to have affinity to Mycobacterium bovis. Furthermore, two CBDs were able to fluorescently label Mycobacterium bovis in milk samples.
BIOCHEMICAL AND BIOPHYSICAL RESEARCH COMMUNICATIONS
(2023)
Review
Chemistry, Medicinal
Cristhian N. Rodriguez-Silva, Igor Muccilo Prokopczyk, Jean Leandro Dos Santos
Summary: Tuberculosis, a highly fatal infectious disease caused by Mycobacterium tuberculosis, remains a global concern with the emergence of drug-resistant strains. The development of new anti-Mtb agents, such as chalcones, is crucial to combat the disease. This review focuses on 37 chalcones that have demonstrated anti-Mtb activity, providing valuable insights for drug design.
MINI-REVIEWS IN MEDICINAL CHEMISTRY
(2022)
Review
Pharmacology & Pharmacy
Mashudu T. Mphaphuli, Mduduzi N. Sithole, Pradeep Kumar, Pierre P. D. Kondiah, Mostafa Mabrouk, Yahya E. Choonara
Summary: This review examines the current use of nanotechnology as a drug delivery system for anti-TB drugs and explores the potential of integrating these nanoparticle systems into bioactive three-dimensional biomaterial scaffolds. This innovative approach has the potential to revolutionize the treatment of bone TB and CNS-TB.
JOURNAL OF DRUG DELIVERY SCIENCE AND TECHNOLOGY
(2023)
Article
Multidisciplinary Sciences
Thanuja D. Sudasinghe, Michael T. Banco, Donald R. Ronning
Summary: EgtD is a crucial enzyme for EGT synthesis in M. tb, and inhibitors targeting this enzyme could potentially shorten Tuberculosis treatment regimens by weakening important bacterial defenses. The inhibitors identified bind in various regions of the enzyme active site, providing structural information for developing more potent inhibitors.
SCIENTIFIC REPORTS
(2021)
Review
Chemistry, Medicinal
Milan Urban, Veronika Slachtova, Lucie Brulikova
Summary: Mycobacterial energy metabolism, particularly the oxidative phosphorylation pathway, has become increasingly important as a molecular target for the development of new anti-TB drugs. Small organic molecules targeting this pathway have shown promising activity against latent and resistant TB strains, with FDA-approved inhibitors confirming the value of targeting mycobacterial energy metabolism.
EUROPEAN JOURNAL OF MEDICINAL CHEMISTRY
(2021)
Article
Polymer Science
Daniele N. Gouveia, Adriana G. Guimaraes, Marlange A. Oliveira, Thallita K. Rabelo, Licia T. S. Pina, Wagner B. R. Santos, Iggo K. S. Almeida, Tatianny A. Andrade, Mairim Russo Serafini, Bruno S. Lima, Adriano A. S. Araujo, Jose Evaldo R. Menezes-Filho, Artur Santos-Miranda, Luciana Scotti, Marcus Tullius Scotti, Henrique Douglas Melo Coutinho, Jullyana S. S. Quintans, Raffaele Capasso, Lucindo J. Quintans-Junior
Summary: Alpha-terpineol nanocapsules (TP-LNC) show potential as a candidate drug for treating chemotherapy-induced peripheral neuropathy. The study finds that TP-LNC has stability and encapsulation efficiency, and can prolong the antihyperalgesic effect when combined with free TP. Furthermore, TP has molecular interactions with different calcium channels, reducing calcium currents.
Article
Chemistry, Applied
Andreza Barbosa Silva Cavalcanti, Mayara Dos Santos Maia, Pedro Thiago Ramalho de Figueiredo, Renata Priscila Barros de Menezes, Alex France Messias Monteiro, Roseana Araujo Ramos Meireles, Gabriela Cristina Soares Rodrigues, Ana Rita Rodrigues de Almeida Silva, Jociano da Silva Lins, Laisa Vilar Cordeiro, Valnes S. Rodrigues Junior, Ana Paula O. T. Castelo Branco, Maria de Fatima Agra, Zoe L. Sessions, Eugene N. Muratov, Luciana Scotti, Marcelo Sobral da Silva, Vicente Carlos de Oliveira Costa, Josean Fechine Tavares, Marcus Tullius Scotti
Summary: Plants of the Hyptidinae subtribe, such as Mesosphaerum sidifolium, have been found to contain bioactive molecules with potential as new drug candidates. In this study, the chemical composition of diterpenes isolated from M. sidifolium was analyzed using NMR spectral data. In silico modeling predicted 48 diterpenes with potential biological activity against Mycobacterium tuberculosis. In vitro testing revealed that four compounds showed antimicrobial activity against M. tuberculosis, with Pomiferin D and 1 exhibiting the strongest effect.
NATURAL PRODUCT RESEARCH
(2023)
Review
Pharmacology & Pharmacy
Teresa Carolliny Moreira Lustoza Rodrigues, Jessica Paiva de Moura, Aline Matilde Ferreira dos Santos, Alex France M. Monteiro, Simone Mendes Lopes, Marcus Tullius Scotti, Luciana Scotti
Summary: Epilepsy is a neurological disease caused by an imbalance of inhibitory and excitatory signaling. Drugs targeting active pathophysiology can be used for treatment. Molecular docking predicts possible pharmacological activities of these targets.
CURRENT DRUG TARGETS
(2023)
Article
Biochemistry & Molecular Biology
Octavio L. Guterres L. Fernandes, Tiago Tizziani, Bibiana P. Dambros, Natalia Ferreira de Sousa, Carime Mansur L. Pontes, Layzon A. L. da Silva, Luiz A. Escorteganha A. Pollo, Francisco F. de Assis, Marcus T. Scotti, Luciana Scotti, Antonio L. Braga, Mario Steindel, Louis P. Sandjo
Summary: This study reports the inhibitory effects of 40 synthetic chalcones against SARS-CoV-2 main protease (M-pro), along with their cytotoxicity, hemolysis, and in silico interactions. Seven compounds showed enzyme inhibition with IC50 ranging from 13.76 to 36.13 μM. Except for compounds 35 and 36, the active compounds were not cytotoxic up to 150 μM. Compounds 10 and 35-39 had no hemolysis, while compound 28 showed weak hemotoxicity at 150 μM. Molecular docking suggested a covalent binding between compound 10 and M-pro, with proximity to cys145 and His41.
CHEMISTRY & BIODIVERSITY
(2023)
Review
Chemistry, Medicinal
Teresa Carolliny Moreira Lustoza Rodrigues, Natalia Ferreira de Sousa, Aline Matilde Ferreira dos Santos, Renan Dantas Aires Guimaraes, Marcus Tullius Scotti, Luciana Scotti
Summary: This study investigated the multi-target effect in neurological disorders through computational techniques. The results suggest that computational methods can identify multiple pharmacologically active targets and propose possible drug candidates with multi-target activity.
CURRENT TOPICS IN MEDICINAL CHEMISTRY
(2023)
Article
Biochemistry & Molecular Biology
Layzon A. Lemos da Silva, Louis P. Sandjo, Laura S. Assuncao, Anne N. Prigol, Carolina D. de Siqueira, Tania B. Creczynski-Pasa, Marcus T. Scotti, Luciana Scotti, Fabiola B. Filippin-Monteiro, Maique W. Biavatti
Summary: This study investigates the sensitivity of semisynthetic sesquiterpene lactone (SL) derivatives by preparing them under different pH conditions and evaluating their anti-inflammatory and antiproliferative activities. Results indicate that some of these derivatives exhibit significant cytotoxic activity and selectivity against human melanoma cells. They also demonstrate the ability to reduce the release of interleukin-6 (IL-6) and nitrite (NOx) in pre-treated macrophages. Overall, the study suggests that acidic and alkaline extraction processes can promote the formation of SLs.
Article
Chemistry, Medicinal
Isadora Silva Luna, Thalisson Amorim de Souza, Marcelo Sobral da Silva, Klinger Antonio da Franca Rodrigues, Luciana Scotti, Marcus Tullius Scotti, Francisco Jaime Bezerra Mendonca-Junior
Summary: In this study, a series of 2-amino-thiophene (2-AT) derivatives were virtually screened and evaluated using cheminformatics tools. Eleven potential anti-leishmanial 2-AT derivatives were identified, which exhibited good activity against the parasite and low cytotoxicity. Ligand-based virtual screening proved to be effective in selecting candidates for the development of new anti-leishmanial agents, and 2-AT derivatives showed promise as hit compounds.
EUROPEAN JOURNAL OF MEDICINAL CHEMISTRY
(2023)
Article
Biochemistry & Molecular Biology
Gopalsamy Rajiv Gandhi, Chelankara Suresh Sharanya, Abhithaj Jayanandan, Madathilkovilakath Haridas, Varghese Edwin Hillary, Sathiyabama Rajiv Gandhi, Gurunagarajan Sridharan, Rengaraju Sivasubramanian, Alan Bruno Silva Vasconcelos, Monalisa Martins Montalvao, Stanislaus Antony Ceasar, Natalia Ferreira de Sousa, Luciana Scotti, Marcus Tullius Scotti, Ricardo Queiroz Gurgel, Lucindo Jose Quintans
Summary: This study screened 18 flavonoids and 8 volatile components from Citrus sinensis peel and found that flavonoids had higher binding probabilities to selected anti-cancer drug targets than volatile components, indicating their potential in developing effective cell proliferation inhibitors. Chlorogenic acid showed the highest binding affinity to important anti-cancer targets iNOS, MMP-9, and p53, suggesting its significant therapeutic potential in cancer treatment with consistent binding mode to multiple drug targets.
JOURNAL OF BIOMOLECULAR STRUCTURE & DYNAMICS
(2023)
Review
Biochemistry & Molecular Biology
Fernando Ferreira Leite, Natalia Ferreira de Sousa, Bruno Hanrry Melo de Oliveira, Gabrielly Diniz Duarte, Maria Denise Leite Ferreira, Marcus Tullius Scotti, Jose Maria Barbosa Filho, Luis Cezar Rodrigues, Ricardo Olimpio de Moura, Francisco Jaime Bezerra Mendonca-Junior, Luciana Scotti
Summary: This study investigated the role of natural and synthetic chalcones and their anticancer activity in vitro reported from 2019 to 2023. The analysis found that the presence of polar radicals such as hydroxyl and methoxyl contributed to the anticancer activity of chalcones derivatives. The results hope to aid in the development of effective drugs to inhibit colon adenocarcinoma.
Editorial Material
Immunology
Luciana Scotti, Jagdish Suresh Patel, Malihe Hassanzadeh, Marcus T. Scotti
FRONTIERS IN CELLULAR AND INFECTION MICROBIOLOGY
(2023)
Article
Oncology
Maria Aparecida da Conceicao de Lira, Marllyn Marques da Silva, Tamiris Alves Rocha, Danielle Feijo de Moura, Erick Caique Santos Costa, Mayara dos Santos Maia, Luciana Scotti, Marcus Tullius Scotti, Maria de Lourdes Lacerda Buril, Eugenia Cristina Pereira, Francisco Carlos Amanajas de Aguiar Junior, Mariane Cajuba de Britto Lira Nogueira, Noemia Pereira da Silva Santos, Emerson Peter da Silva Falcao, Sebastiao Jose de Melo
Summary: The study evaluated the antitumour potential of a depsidone isolated from Parmotrema concurrens, salazinic acid (SAL), through in vitro, in vivo, and in silico studies. The results demonstrated that SAL showed low cytotoxicity to cancer cell lines and had high tumour inhibition activity in both in vitro and in vivo experiments. Molecular dynamics simulations revealed that SAL had stronger enzymatic interaction capacity with human thymidylate synthase compared to 5-fluorouracil. The findings suggest that salazinic acid has potential as a tumour inhibition agent.
ANTI-CANCER AGENTS IN MEDICINAL CHEMISTRY
(2023)
Article
Chemistry, Medicinal
Poliana Gomes de Abrantes, Paloma Gomes de Abrantes, Damiao Alves dos Santos Silva, Renata Rodrigues Magalhaes, Paulo Bruno Norberto da Silva, Gardenia Carmen Gadelha Militao, Renata Priscila Barros de Menezes, Luciana Scotti, Marcus Tullius Scotti, Juliana Alves Vale
Summary: This work investigated solvents for the catalyst-free synthesis of 2-amino-4H-chromenes from salicylaldehydes and malononitrile. The use of ethanol under reflux conditions resulted in the production of several 2-amino-4H-chromenes with high yields and short reaction time. Virtual screening and in vitro assays demonstrated the high potential of compound 5e as an antitumor agent, suggesting a possible mechanism of action involving inhibition of the mutant T315l Abl protein. This study provides a promising starting point for the development of new antitumor agents.
MEDICINAL CHEMISTRY RESEARCH
(2023)
Article
Biochemistry & Molecular Biology
Mayara dos Santos Maia, Francisco Jaime Bezerra Mendonca-Junior, Gabriela Cristina Soares Rodrigues, Adriano Soares da Silva, Niara Isis Pereira de Oliveira, Pablo Rayff da Silva, Cicero Francisco Bezerra Felipe, Ana Pavla Almeida Diniz Gurgel, Anuraj Nayarisseri, Marcus Tullius Scotti, Luciana Scotti
Summary: Cancer, a complex disease, is on the rise. Lignans, known for their anticancer properties, pose challenges in identifying specific subclasses with antitumor activity due to their structural diversity. This study aimed to explore the association between lignan subclasses and antitumor activity while considering the genetic profile of targeted variants. Predictive models were built for different targets, and molecular docking was performed to evaluate the binding energy of lignans with the best predicted biological activity. The results highlighted dibenzocyclooctadiene, furofuran, and aryltetralin subclasses as exhibiting strong anticancer activity.
