Mini Reviews in Medicinal Chemistry - Volume 25, Issue 16, 2025

Poor water solubility limits the bioavailability, absorption, and efficacy of many drugs, especially BCS class II and IV compounds. Polymeric drug conjugation (PDC) is a promising strategy to overcome these challenges by chemically linking hydrophobic drugs with hydrophilic polymers via covalent or non-covalent bonds. This enhances aqueous solubility, stability, and bioavailability, leading to improved therapeutic effects and reduced adverse reactions. PDC prolongs drug circulation, ensuring consistent absorption at lower doses. This article focuses on how this strategy can address solubility issues and enhance drug delivery effectiveness, it also brings spotlight to investigate current advancements in the field of polymer drug conjugates. Following a structured approach guided by PRISMA, relevant research on polymeric conjugation strategies were identified by screening literature from PubMed, Scopus, and Google Scholar etc. Key polymers such as PEG, PLGA, HPMA, chitosan, and dextran etc were investigated for their solubility-enhancing capability. Clinical studies validate its success, making it a novel approach to addressing solubility related pharmaceutical challenges.

The diagnosis of adrenocortical tumors remains clinically challenging due to overlapping morphological and functional features between benign, malignant, and hormonally active lesions. Malignant and functional tumors are frequently associated with poor prognosis. Traditional morphological imaging methods, such as CT and MRI, cannot reliably distinguish lesion types. Recent evidence suggests that molecular imaging targeting C-X-C motif chemokine receptor 4 (CXCR4), a biomarker overexpressed in functional adenomas and adrenocortical carcinomas (ACC), offers enhanced diagnostic precision. For instance, ⁶⁸Ga-pentixafor, a CXCR4-targeted radiotracer, demonstrates high accuracy in distinguishing functional from nonfunctional lesions and unilateral from bilateral subtypes in primary aldosteronism. Depending on the level of tracer uptake, it may also be possible to guide therapeutic decisions and assess treatment response. For Cushing's syndrome, particularly cortisol-producing adenomas, CXCR4 imaging facilitates the localization of adrenal lesions, reducing dependency on invasive techniques. In ACC, overexpression of CXCR4 enables metastasis detection, and its complementary use with ¹⁸F-FDG PET/CT improves lesion detection. Furthermore, the theranostic agent ¹⁷⁷Lu/⁹⁰Y-Pentixather demonstrates considerable promise for CXCR4-directed Endoradiotherapy (ERT) in advanced ACC. This review aimed to summarize the advancements of CXCR4-targeted molecular imaging in adrenocortical tumors and ERT in ACC.

Quinoxalines are a versatile class of nitrogen-containing heterocyclic compounds that have been extensively studied for their diverse pharmacological properties. Recently, interest has grown in exploring quinoxaline derivatives for applications in oral health, driven by their unique mechanisms of action and potential to address major challenges in dental medicine. This review comprehensively examines the recent progress in the development of quinoxaline-based compounds targeting oral pathogens responsible for dental caries, periodontitis, and other biofilm-associated diseases. Beyond their antimicrobial effects, quinoxalines also exhibit anti-inflammatory properties by modulating key molecular pathways implicated in periodontal inflammation, thereby offering a dual therapeutic potential. Moreover, their incorporation as functional additives in restorative dental materials is emerging, aiming to enhance antimicrobial efficacy and improve material performance. Despite promising in vitro and in vivo data, several critical barriers must be overcome before clinical translation can be realized. These include ensuring biocompatibility with oral tissues, achieving formulation stability under the dynamic conditions within the oral environment, and optimizing delivery systems to ensure targeted, sustained release at the site of action. This review highlights current strategies to address these challenges and proposes directions for future research, including advanced formulation technologies and comprehensive preclinical evaluations. Ultimately, quinoxaline derivatives hold significant promise as multifunctional agents capable of integrating antimicrobial, anti-inflammatory, and biomaterial-enhancing properties to improve oral health outcomes. This synthesis of current knowledge supports continued investigation into quinoxalines as novel therapeutics and functional components for dental care.

The increasing resistance of causative agents to current treatments has made infectious disease management more challenging. Heterocyclic compounds have garnered considerable attention due to their numerous significant medical and biological applications. Research interest in heterocyclic compounds is rapidly increasing due to extensive synthetic studies and their functional utility. Phenothiazine (PTZ), an organic thiazine compound, has a broad range of biological activities, including antimicrobial, antimalarial, antipsychotic, anti-inflammatory, and antiemetic effects. Additionally, modifications to the phenothiazine structure have enhanced its efficacy, making it a potential candidate for addressing drug-resistant infections. This review examines recent synthesis methods, including catalytic and microwave-assisted techniques, which have expanded the applications of phenothiazine derivatives. The article also discusses structure-activity relationships, which help optimize the pharmacological properties of these compounds for future therapeutic use.