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Pharmaceuticals
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Advances in Drug Analysis and Drug Development
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Advances in Drug Analysis and Drug Development

A special issue of Pharmaceuticals (ISSN 1424-8247). This special issue belongs to the section "Pharmaceutical Technology".

Deadline for manuscript submissions: closed (25 February 2025) | Viewed by 16264

Special Issue Editors

Dr. Daniela Amidžić Klarić

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Guest Editor
Faculty of Pharmacy of Biochemistry, University of Zagreb, A. Kovačića 1, 10000 Zagreb, Croatia
Interests: pharmaceutical analysis, supplement analysis; sample preparation; atomic spectroscopy; chromatography; food analytical chemistry; food control; bioactive compounds; metals
Special Issues, Collections and Topics in MDPI journals
Prof. Dr. Ana Mornar

E-Mail Website
Guest Editor
Faculty of Pharmacy of Biochemistry, University of Zagreb, A. Kovačića 1, 10000 Zagreb, Croatia
Interests: drug development; sample preparation; pharmaceutical analysis; bioanalysis; biopharmaceutical analysis; food analysis; chromatography; mass spectrometry
Special Issues, Collections and Topics in MDPI journals

Special Issue Information

Dear Colleagues,

The different phases of drug development include preclinical and clinical drug development. During this long-term process, a large number of different compounds (active pharmaceutical substances, excipients, impurities and metabolites) are monitored, and the development of new analytical methods facilitates the implementation.

This Special Issue of Pharmaceuticals will be a collection of research articles, short communications and reviews related to original and novel analytical methods developed for the evaluation of active substances in various dosage forms during drug development.

From the analytical point of view, a special challenge is the identification and determination of metabolites, as the products of drug metabolism, and other endogenous compounds. Green and sustainable analytical procedures are more than welcome, as well as methods, including the pre-treatment of different dosage forms and biological materials as samples.

The coverage of this Special Issue includes, but is not limited to:

  • Advances in instrumental analysis in drug development;
  • Preformulation and pharmaceutical formulation studies;
  • Preclinical and clinical evaluation of formulation technologies;
  • The pharmacokinetic analysis of active substances and metabolites;
  • Innovative processing and analytical technologies;
  • Extractable and leachable testing in pharmaceutical analysis;
  • Bioanalysis of nano-drug delivery systems;
  • Lab-on-chip technology;
  • High-throughput screening in preformulation studies;
  • Validation and regulatory aspects in pharmaceutical analysis.

We are looking forward to hearing from you.

Dr. Daniela Amidžić Klarić
Prof. Dr. Ana Mornar
Guest Editors

Manuscript Submission Information

Manuscripts should be submitted online at www.mdpi.com by registering and logging in to this website. Once you are registered, click here to go to the submission form. Manuscripts can be submitted until the deadline. All submissions that pass pre-check are peer-reviewed. Accepted papers will be published continuously in the journal (as soon as accepted) and will be listed together on the special issue website. Research articles, review articles as well as short communications are invited. For planned papers, a title and short abstract (about 100 words) can be sent to the Editorial Office for announcement on this website.

Submitted manuscripts should not have been published previously, nor be under consideration for publication elsewhere (except conference proceedings papers). All manuscripts are thoroughly refereed through a single-blind peer-review process. A guide for authors and other relevant information for submission of manuscripts is available on the Instructions for Authors page. Pharmaceuticals is an international peer-reviewed open access monthly journal published by MDPI.

Please visit the Instructions for Authors page before submitting a manuscript. The Article Processing Charge (APC) for publication in this open access journal is 2900 CHF (Swiss Francs). Submitted papers should be well formatted and use good English. Authors may use MDPI's English editing service prior to publication or during author revisions.

Keywords

  • analytical methodology

  • chromatographic techniques
  • spectrometric techniques
  • thermal analysis techniques
  • sample preparation
  • drug stability
  • compatibility study
  • bioavailability studies
  • therapeutic drug monitoring
  • quality by design in pharmaceutical analysis

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  • Greater discoverability: Special Issues support the reach and impact of scientific research. Articles in Special Issues are more discoverable and cited more frequently.
  • Expansion of research network: Special Issues facilitate connections among authors, fostering scientific collaborations.
  • External promotion: Articles in Special Issues are often promoted through the journal's social media, increasing their visibility.
  • e-Book format: Special Issues with more than 10 articles can be published as dedicated e-books, ensuring wide and rapid dissemination.

Further information on MDPI's Special Issue policies can be found here.

Published Papers (10 papers)

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Research

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24 pages, 4123 KiB  
Article
Developing a Chromatographic Method for Quantifying Latanoprost and Related Substances in Glaucoma Treatments
by Katarzyna Asendrych-Wicik, Katarzyna Malik and Magdalena Markowicz-Piasecka
Pharmaceuticals 2025, 18(5), 619; https://doi.org/10.3390/ph18050619 - 24 Apr 2025
Viewed by 294
Abstract
Background/Objectives: Latanoprost is a leading active pharmaceutical ingredient belonging to the synthetic prostaglandin F2α analogs, widely used as a first-line treatment for open-angle glaucoma and increased intraocular pressure. This study addresses the critical need for an accurate and precise chromatographic method that [...] Read more.
Background/Objectives: Latanoprost is a leading active pharmaceutical ingredient belonging to the synthetic prostaglandin F2α analogs, widely used as a first-line treatment for open-angle glaucoma and increased intraocular pressure. This study addresses the critical need for an accurate and precise chromatographic method that is capable of simultaneously quantifying latanoprost and six latanoprost-related substances in antiglaucoma eye drops. This will be crucial for patient safety and treatment efficacy. This method enables the separation of latanoprost isomers, (15S)-latanoprost, latanoprost enantiomer, and 5,6-trans latanoprost from latanoprost signal. Furthermore, it is specific for the well-known latanoprost degradants—the major latanoprost acid and the minor 15-ketolatanoprost—as well as synthetic derivatives, such as triphenylphosphine oxide (TPPO) and propan-2-yl 5-(diphenylphosphoryl)pentanoate (IDPP). Using forced degradation studies using high temperatures, UV light, alkalis, acids, and oxidizing agents, the degradation profiles of the drugs were characterized and the method’s stability-indicating power was confirmed. Methods: Separation was achieved on a stationary combined system comprising chiral and cyano columns. Reverse-phase gradient elution and UV 210 nm detection were employed. The novel method was validated according to the European Medicines Agency International Council for Harmonisation Q2 Validation of analytical procedures—Scientific guideline. Results: The method was shown to be linear in the range of 40–60 µg/mL for latanoprost and 0.05–2.77 µg/mL for related substances, confirmed by a correlation coefficient of r = 0.999. Recoveries for latanoprost were obtained within the range of 98.0–102.0% for assays and 90.0–110.0% for impurities. The detection and quantification limits for latanoprost were 0.025 µg/mL and 0.35 µg/mL, respectively. Conclusions: The analytical procedure developed is adequately sensitive, precise, and accurate compared to existing methods. The method can be reliably used to control the critical quality attributes of low-dose latanoprost products, ensuring their required high pharmaceutical quality, which translates into improvements in patient care. This advancement holds significant implications for enhancing the therapeutic management of glaucoma, ensuring drug safety and efficacy. Full article
(This article belongs to the Special Issue Advances in Drug Analysis and Drug Development)
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15 pages, 2025 KiB  
Article
Establishing Multi-Dimensional LC-MS Systems for Versatile Workflows to Analyze Therapeutic Antibodies at Different Molecular Levels in Routine Operations
by Katrin Heinrich, Sina Hoelterhoff, Saban Oezipek, Martin Winter, Tobias Rainer, Lucas Hourtoulle, Ingrid Grunert, Tobias Graf, Michael Leiss and Anja Bathke
Pharmaceuticals 2025, 18(3), 401; https://doi.org/10.3390/ph18030401 - 12 Mar 2025
Viewed by 588
Abstract
Background/Objectives: Multi-dimensional liquid chromatography coupled with mass spectrometry (mD-LC-MS) has emerged as a powerful technique for the in-depth characterization of biopharmaceuticals by assessing chromatographically resolved product variants in a streamlined and semi-automated manner. The study aims to demystify and enhance the accessibility to [...] Read more.
Background/Objectives: Multi-dimensional liquid chromatography coupled with mass spectrometry (mD-LC-MS) has emerged as a powerful technique for the in-depth characterization of biopharmaceuticals by assessing chromatographically resolved product variants in a streamlined and semi-automated manner. The study aims to demystify and enhance the accessibility to this powerful but inherently complex technique by detailing a robust and user-friendly instrument platform, allowing analysts to switch seamlessly between intact, subunit, and peptide mapping workflows. Methods: Starting from a commercially available Two-Dimensional Liquid Chromatography (2D-LC) system, we introduce specific hardware and software extensions leading to two versatile mD-LC-MS setups, in slightly different configurations. The technique’s efficacy is demonstrated through a case study on a cation exchange chromatography method assessing the charge variants of a bispecific antibody, isolating peak(s) of interest, followed by online sample processing, including reduction and enzymatic digestion, and subsequently mass spectrometry analysis. Results: The accuracy and reproducibility of both mD-LC-MS setups proposed in this study were successfully tested. Despite the complex peak patterns in the first dimension, the systems were equally effective in identifying and quantifying the underlying product species. This case study highlights the routine usability of mD-LC-MS technology for the characterization of (ultra) high-performance liquid chromatography (UHPLC) of therapeutic biomolecule. Conclusions: The demonstrated reliability and accuracy underscore the practicality of mD-LC-MS for routine use in biopharmaceutical analysis. Our detailed description of the mD-LC-MS systems and insights simplify access to this advanced technology for a broader scientific community, regardless of expertise level, and lower the entry barrier for its use in various research and industrial settings. Full article
(This article belongs to the Special Issue Advances in Drug Analysis and Drug Development)
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18 pages, 3812 KiB  
Article
The Stability-Indicating Ultra High-Performance Liquid Chromatography with Diode Array Detector and Tandem Mass Spectrometry Method Applied for the Forced Degradation Study of Ritlecitinib: An Appraisal of Green and Blue Metrics
by Jelena Kovačić, Daniela Amidžić Klarić, Nikša Turk, Željko Krznarić, Emma Riordan and Ana Mornar
Pharmaceuticals 2025, 18(1), 124; https://doi.org/10.3390/ph18010124 - 17 Jan 2025
Viewed by 1250
Abstract
Background/Objectives: Janus kinase inhibitors open new horizons for small-molecule drugs in treating inflammatory bowel disease, with ritlecitinib demonstrating significant efficacy in clinical trials for ulcerative colitis and Crohn’s disease. Ritlecitinib, a second-generation JAK3 inhibitor, is a novel therapeutic agent for alopecia areata and [...] Read more.
Background/Objectives: Janus kinase inhibitors open new horizons for small-molecule drugs in treating inflammatory bowel disease, with ritlecitinib demonstrating significant efficacy in clinical trials for ulcerative colitis and Crohn’s disease. Ritlecitinib, a second-generation JAK3 inhibitor, is a novel therapeutic agent for alopecia areata and other autoimmune conditions. Methods: A new stability-indicating UHPLC-DAD-MS/MS method was developed, validated, and applied for a forced degradation study of ritlecitinib under ICH guidelines. Results: The method demonstrated high specificity, sensitivity (LOD: 0.04 µg/mL; LOQ: 0.14 µg/mL), precision (RSD ≤ 0.15%), and accuracy (99.9–100.3%). Forced degradation studies under acidic, basic, oxidative, thermal, and photolytic conditions revealed four novel degradation products. Basic degradation followed second-order kinetics, while oxidative degradation followed zero-order kinetics. Conclusions: The validated method reliably characterized ritlecitinib’s stability and degradation products, providing essential data for optimizing formulation, determining proper storage conditions, anticipating drug–excipient interactions, and ensuring quality control. The eco-friendliness and applicability of the developed forced degradation procedure were evaluated using various green and blue metric tools. Incorporating green analytical principles underscores its potential for sustainable pharmaceutical analysis. Full article
(This article belongs to the Special Issue Advances in Drug Analysis and Drug Development)
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19 pages, 1102 KiB  
Article
Exploring the Feasibility of a Bracketing Approach Utilizing Modeling for Development of Long-Acting Injectables for Regulatory Approval—A Case Study Using Levonorgestrel
by Susan Cole, Henry Pertinez, Andrew S. Butler, Essam Kerwash, Swati Bhat, Eman El-Khateeb and Andrew Owen
Pharmaceuticals 2024, 17(12), 1640; https://doi.org/10.3390/ph17121640 - 6 Dec 2024
Viewed by 1164
Abstract
Background: The development of long-acting products of a characterized drug substance is of great interest. It is possible to support the development of these products with available clinical data by matching the exposure to a predefined bracket of a minimal concentration for efficacy [...] Read more.
Background: The development of long-acting products of a characterized drug substance is of great interest. It is possible to support the development of these products with available clinical data by matching the exposure to a predefined bracket of a minimal concentration for efficacy and a maximal concentration for safety. This bracketing approach would cut down on the time and cost of new long-acting contraceptive products progressing to market. The current study describes the assessment of the data available to support a bracketing approach to conclude comparable levels of efficacy and safety for a postulated novel long-acting reversible contraceptive (LARC) product of levonorgestrel. Methods: Literature evidence of levonorgestrel efficacy, as quantified by the Pearl Index, was utilized and modeled by incorporating three LARC products for the estimation of a minimal concentration required for efficacy. Further literature was reviewed to quantify the maximal concentration required to ensure product safety. Additionally, a review of the regulatory precedence for the approach was conducted using European and UK databases. Results: There was a reasonable definition of the minimal concentrations for efficacy where the target concentrations of levonorgestrel were in the range of 200–400 pg/mL. Maximum concentrations for safety were less well defined. Although regulatory guidance supports the bracketing approach, there is little precedence for licensing new products based on pharmacokinetic data only, despite much reduced clinical and non-clinical packages being evidenced. Conclusions: Understanding of the exposure response is not currently considered sufficient to support a bracketing approach for a new levonorgestrel product. If additional safety data are established, current regulations may allow for a reduced application package. Additional work is needed to support the approach, and this could utilize the wealth of information in real-world datasets combined with systems models. Full article
(This article belongs to the Special Issue Advances in Drug Analysis and Drug Development)
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11 pages, 1411 KiB  
Article
Effect of Citric Acid and Tromethamine on the Stability of Eyedrops Containing Lifitegrast
by Ji-Su Jeong, Eun-Sol Ha, Heejun Park, Seon-Kwang Lee, Hui-Taek Kang and Min-Soo Kim
Pharmaceuticals 2024, 17(11), 1415; https://doi.org/10.3390/ph17111415 - 23 Oct 2024
Viewed by 1962
Abstract
Background/Objectives: Lifitegrast is an effective treatment for dry eye disease, reducing inflammation and improving the ocular surface condition. Owing to its high sensitivity to oxidation and hydrolysis, formulation studies are required to maintain the physicochemical stability of lifitegrast. This study aimed to overcome [...] Read more.
Background/Objectives: Lifitegrast is an effective treatment for dry eye disease, reducing inflammation and improving the ocular surface condition. Owing to its high sensitivity to oxidation and hydrolysis, formulation studies are required to maintain the physicochemical stability of lifitegrast. This study aimed to overcome the instability of lifitegrast by developing a more stable eyedrop formulation by using citric acid and tromethamine to prevent the degradation of lifitegrast. Methods: Based on the Design of Experiment (DoE) approach, formulations were prepared at various concentrations of two stabilizers, citric acid and tromethamine. The stabilizers were carefully controlled to reduce the generation of degradation products. The eyedrops were stored under accelerated test conditions, and parameters such as appearance, pH, drug content, and impurities were evaluated. Results: The results showed that all critical quality attributes (CQAs) including appearance, pH, drug content, and impurities were maintained at stable levels under accelerated conditions, meeting established criteria. In addition, it was suggested that citric acid provided protection against oxidative stress, while tromethamine prevented hydrolysis caused by pH fluctuations. Conclusions: Consequently, it was concluded that the developed lifitegrast-containing eyedrop formulation exhibited improved physicochemical stability, validated through statistical analyses. These findings contribute to the development of stable eyedrops and provide a foundation for commercial production and clinical applications. Full article
(This article belongs to the Special Issue Advances in Drug Analysis and Drug Development)
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17 pages, 11924 KiB  
Article
Auranofin as a Novel Anticancer Drug for Anaplastic Thyroid Cancer
by Seung-Chan An, Hak Hoon Jun, Kyeong Mi Kim, Issac Kim, Sujin Choi, Hyunjeong Yeo, Soonchul Lee and Hyun-Ju An
Pharmaceuticals 2024, 17(10), 1394; https://doi.org/10.3390/ph17101394 - 18 Oct 2024
Cited by 1 | Viewed by 1838
Abstract
Background/Objectives: Anaplastic thyroid cancer (ATC) is an aggressive and rare cancer with a poor prognosis, and traditional therapies have limited efficacy. This study investigates drug repositioning, focusing on auranofin, a gold-based drug originally used for rheumatoid arthritis, as a potential treatment for ATC. [...] Read more.
Background/Objectives: Anaplastic thyroid cancer (ATC) is an aggressive and rare cancer with a poor prognosis, and traditional therapies have limited efficacy. This study investigates drug repositioning, focusing on auranofin, a gold-based drug originally used for rheumatoid arthritis, as a potential treatment for ATC. Methods: Auranofin was identified from an FDA-approved drug library and tested on two thyroid cancer cell lines, 8505C and FRO. Antitumor efficacy was evaluated through gene and protein expression analysis using Western blot, FACS, and mRNA sequencing. In vivo experiments were conducted using subcutaneous injections in nude mice to confirm the anticancer effects of auranofin. Results: Auranofin induced reactive oxygen species (ROS) production and apoptosis, leading to a dose-dependent reduction in cell viability, G1/S phase cell cycle arrest, and altered expression of regulatory proteins. It also inhibited cancer stem cell activity and suppressed epithelial–mesenchymal transition. mRNA sequencing revealed significant changes in the extracellular matrix–receptor interaction pathway, supported by Western blot results. In vivo xenograft models demonstrated strong antitumor activity. Conclusions: Auranofin shows promise as a repurposed therapeutic agent for ATC, effectively inhibiting cell proliferation, reducing metastasis, and promoting apoptosis. These findings suggest that auranofin could play a key role in future ATC treatment strategies. Full article
(This article belongs to the Special Issue Advances in Drug Analysis and Drug Development)
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21 pages, 598 KiB  
Article
RP-CAD for Lipid Quantification: Systematic Method Development and Intensified LNP Process Characterization
by Nicole Beckert, Annabelle Dietrich and Jürgen Hubbuch
Pharmaceuticals 2024, 17(9), 1217; https://doi.org/10.3390/ph17091217 - 16 Sep 2024
Cited by 1 | Viewed by 2129
Abstract
Lipid nanoparticles (LNPs) and their versatile nucleic acid payloads bear great potential as delivery systems. Despite their complex lipid composition, their quality is primarily judged by particle characteristics and nucleic acid encapsulation. In this study, we present a holistic reversed-phase (RP)-charged aerosol detection [...] Read more.
Lipid nanoparticles (LNPs) and their versatile nucleic acid payloads bear great potential as delivery systems. Despite their complex lipid composition, their quality is primarily judged by particle characteristics and nucleic acid encapsulation. In this study, we present a holistic reversed-phase (RP)-charged aerosol detection (CAD)-based method developed for commonly used LNP formulations, allowing for intensified LNP and process characterization. We used an experimental approach for power function value (PFV) optimization termed exploratory calibration, providing a single PFV (1.3) in an appropriate linearity range for all six lipids. Followed by the procedure of method calibration and validation, linearity (10–400 ng, R2 > 0.996), precision, accuracy, and robustness were effectively proven. To complement the commonly determined LNP attributes and to evaluate the process performance across LNP processing, the developed RP-CAD method was applied in a process parameter study varying the total flow rate (TFR) during microfluidic mixing. The RP-CAD method revealed a constant lipid molar ratio across processing but identified deviations in the theoretical lipid content and general lipid loss, which were both, however, entirely TFR-independent. The deviations in lipid content could be successfully traced back to the lipid stock solution preparation. In contrast, the observed lipid loss was attributable to the small-scale dialysis following microfluidic mixing. Overall, this study establishes a foundation for employing RP-CAD for lipid quantification throughout LNP processing, and it highlights the potential to extend its applicability to other LNPs, process parameter studies, or processes such as cross-flow filtration. Full article
(This article belongs to the Special Issue Advances in Drug Analysis and Drug Development)
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21 pages, 4899 KiB  
Article
Development of Analytical Method for the Quantitation of Monoclonal Antibodies Solutions via Raman Spectroscopy: The Case of Bevacizumab
by Michail Lykouras, Panagiota Papaspyridakou, Olga E. Makri, Constantine D. Georgakopoulos and Malvina G. Orkoula
Pharmaceuticals 2024, 17(4), 446; https://doi.org/10.3390/ph17040446 - 29 Mar 2024
Viewed by 1691
Abstract
Personalized dosages of monoclonal antibodies are being used more regularly to treat various diseases, rendering their quantitation more essential than ever for the right dose administration to the patients. A promising alternative, which overcomes the obstacles of the well-established chromatographic techniques regarding the [...] Read more.
Personalized dosages of monoclonal antibodies are being used more regularly to treat various diseases, rendering their quantitation more essential than ever for the right dose administration to the patients. A promising alternative, which overcomes the obstacles of the well-established chromatographic techniques regarding the quantification of biopharmaceuticals, is Raman spectroscopy. This study aimed to develop and validate a novel analytical method for the quantitation of bevacizumab in solutions via Raman spectroscopy. For this purpose, a droplet of the solution was left to dry on a highly reflective carrier and a home-made apparatus was employed for rotation of the sample. Hence, each recorded Raman spectrum was the average of the signal acquired simultaneously from multiple points on a circular circumference. The method was validated, and the detection limit of the antibody was found to be 1.06 mg/mL. Bevacizumab was found to be highly distributed at the formed coffee ring of the dried droplet, though this was a function of solution concentration. Finally, Raman spectra at different distances on the coffee ring were obtained from the four quarters. The lowest bevacizumab detection limit was found at a distance of 75 μm from the external side of the coffee ring and it was determined to be equal to 0.53 mg/mL. Full article
(This article belongs to the Special Issue Advances in Drug Analysis and Drug Development)
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19 pages, 3273 KiB  
Article
The Study on Timolol and Its Potential Phototoxicity Using Chemical, In Silico and In Vitro Methods
by Karolina Lejwoda, Anna Gumieniczek, Agata Filip and Beata Naumczuk
Pharmaceuticals 2024, 17(1), 98; https://doi.org/10.3390/ph17010098 - 11 Jan 2024
Cited by 1 | Viewed by 1977
Abstract
Timolol (TIM) is a non-selective ß-adrenergic receptor antagonist used orally for the treatment of hypertension and heart attacks, and topically for treating glaucoma; lately, it has also been used in some specific dermatological problems. In the present study, its photodegradation and potential risk [...] Read more.
Timolol (TIM) is a non-selective ß-adrenergic receptor antagonist used orally for the treatment of hypertension and heart attacks, and topically for treating glaucoma; lately, it has also been used in some specific dermatological problems. In the present study, its photodegradation and potential risk of phototoxicity were examined using chemical, in silico and in vitro methods. The UV/VIS irradiated solutions of TIM at pH 1–13 were subjected to LC-UV and UPLC-HRMS/MS analyses showing pseudo first-order kinetics of degradation and several degradation products. The structures of these photodegradants were elucidated by fragmentation path analysis based on high resolution (HR) fragmentation mass spectra, and then used for toxicity evaluation using OSIRIS Property Explorer and Toxtree. Potential risk of phototoxicity was also studied using chemical tests for detecting ROS under UV/VIS irradiation and in vitro tests on BALB/c 3T3 mouse fibroblasts (MTT, NRU and Live/Dead tests). TIM was shown to be potentially phototoxic because of its UV/VIS absorptive properties and generation ROS during irradiation. As was observed in the MTT and NRU tests, the co-treatment of fibroblasts with TIM and UV/VIS light inhibited cell viability, especially when concentrations of the drug were higher than 50 µg/mL. Full article
(This article belongs to the Special Issue Advances in Drug Analysis and Drug Development)
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Review

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32 pages, 4126 KiB  
Review
Targeting the Heart of Mycobacterium: Advances in Anti-Tubercular Agents Disrupting Cell Wall Biosynthesis
by Ahmad Diab, Henry Dickerson and Othman Al Musaimi
Pharmaceuticals 2025, 18(1), 70; https://doi.org/10.3390/ph18010070 - 9 Jan 2025
Viewed by 2005
Abstract
Mycobacterium tuberculosis infections continue to pose a significant global health challenge, particularly due to the rise of multidrug-resistant strains, random mycobacterial mutations, and the complications associated with short-term antibiotic regimens. Currently, five approved drugs target cell wall biosynthesis in Mycobacterium tuberculosis. This [...] Read more.
Mycobacterium tuberculosis infections continue to pose a significant global health challenge, particularly due to the rise of multidrug-resistant strains, random mycobacterial mutations, and the complications associated with short-term antibiotic regimens. Currently, five approved drugs target cell wall biosynthesis in Mycobacterium tuberculosis. This review provides a comprehensive analysis of these drugs and their molecular mechanisms. Isoniazid, thioamides, and delamanid primarily disrupt mycolic acid synthesis, with recent evidence indicating that delamanid also inhibits decaprenylphosphoryl-β-D-ribose-2-epimerase, thereby impairing arabinogalactan biosynthesis. Cycloserine remains the sole approved drug that inhibits peptidoglycan synthesis, the foundational layer of the mycobacterial cell wall. Furthermore, ethambutol interferes with arabinogalactan synthesis by targeting arabinosyl transferase enzymes, particularly embB- and embC-encoded variants. Beyond these, six promising molecules currently in Phase II clinical trials are designed to target arabinan synthesis pathways, sutezolid, TBA 7371, OPC-167832, SQ109, and both benzothiazinone derivatives BTZ043 and PBTZ169, highlighting advancements in the development of cell wall-targeting therapies. Full article
(This article belongs to the Special Issue Advances in Drug Analysis and Drug Development)
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