Archiv der Pharmazie最新文献

A series of novel quinazoline-4-one/chalcone hybrids (4a–4j) were synthesized and evaluated as epidermal growth factor receptor (EGFR) inhibitors with anticancer activity. The target compounds were in vitro tested against MCF-7 and HepG2 cancer cell lines, and the EGFR enzyme. Compounds 4a and 4g were the most potent EGFR inhibitors (IC_50 = 0.09 µM and 0.10 µM, respectively), compared to the standard erlotinib (IC₅₀ = 0.16 µM). Also, they exhibited anticancer activity against both cell lines. They were found to induce cell cycle arrest and apoptosis in MCF-7 and HepG2 cancer cells. Molecular docking revealed that, compounds 4a and 4g bind to the active site of EGFR with the Lys A721 amino acid residue in a manner analogous to Erlotinib. This binding interaction likely contributes to their significant biological activity. Further, dynamic stimulation study that is conducted for compounds 4a and 4g, supports their potency as therapeutic agents in cancer treatment.

Gastrointestinal (GI) cancers represent a major global health burden due to their high incidence and mortality. Brusatol has emerged as a promising natural anticancer agent with potent activity against diverse malignancies. It exerts antitumor effects by inhibiting the nuclear factor erythroid 2–related factor 2 (NRF2) signaling pathway, modulating redox homeostasis, and sensitizing tumor cells to oxidative stress and chemotherapeutics. This review summarizes the current understanding of the molecular mechanisms of brusatol in GI cancers, and its synergistic potential with conventional therapies as well as nanotechnology-based delivery systems. We highlight the future directions for safer and more selective brusatol derivatives for GI cancer therapy.

Halogens are utilized in drug discovery and development due to their ability to precisely tune the molecular properties of drug candidates. The halogen substituents play a crucial role in determining the stability, lipophilicity, and receptor binding, as well as significantly influencing the metabolic fate of the drug candidates. Literature insights reveal that 30% of all small molecules approved by the USFDA carry a halogen as a substituent. Considering the vital importance of halogen-containing substituents, we have compiled concise information on halogen-containing US FDA-approved drugs over the last decade (2019–2024). The articles provide information on pharmacological conditions, targets, available formulations, and pharmacokinetic details for each approved drug that possesses a halogen as a substituent, along with its corresponding chemical structure. The analysis revealed that 37 new drugs were approved to combat cancer (13), followed by rare diseases (6), viral infections (3), and other conditions during the analysis period. Furthermore, the chemistry of halogens, along with their medicinal applications, provides key evidence on how halogens have been explored to enhance the pharmacokinetics and pharmacodynamics of drug candidates. The analysis of approved dosage forms revealed that 23 were solid dosage forms, comprising 24 tablet forms, 8 capsules, and 1 powder. CYP3A4 is a major contributor in the metabolism of 6 drugs, followed by CYP3A (3), CYP1A2 (2), CYP3A4/5 (2), and one each by CYP2C9, UGT1A9, CYP2C8, aldehyde oxidase, and other non-CYP enzymes. The present medicinal chemistry perspective is thus expected to be a valuable read for the medicinal and allied sciences community.

Colorectal cancer (CRC), a malignant tumor originating from the colon or rectum epithelium, is one of the most prevalent and lethal gastrointestinal cancers globally, with its pathogenesis closely linked to genetic mutations and dysregulated oncogenic pathways. Despite advances in traditional chemotherapeutics and targeted therapies, CRC still faces challenges such as high metastasis rates, drug resistance, and poor prognosis for advanced-stage patients, highlighting the need for novel therapeutic agents. Indole hybrids offer notable advantages in CRC therapy, as their structural flexibility enables the simultaneous targeting of multiple CRC-related oncogenic pathways and mutated proteins. Optimized modifications enhance target binding affinity, boost antiproliferative/pro-apoptotic activity, and improve pharmacokinetic profiles compared with traditional indole derivatives. Additionally, their multifunctional mechanism helps overcome drug resistance by bypassing cancer cell adaptive changes, and structural refinement reduces off-target toxicity. Accordingly, indole hybrids represent highly valuable molecular scaffolds for the discovery and development of novel therapeutic candidates against CRC. This review outlines the current landscape of indole hybrids with therapeutic potential against CRC, developed from 2021 to the present, aiming to open new avenues for the exploration of novel CRC therapeutic candidates.

Anticoagulation is the cornerstone for preventing thrombosis in coronary heart disease patients with atrial fibrillation or a mechanical heart valve. Guanxinjing formula (GXJF) demonstrates anticoagulant effects, while its anticoagulant substances and mechanisms remain unclear. In this study, the chemical composition of GXJF was identified, establishing a chemical basis for the discovery of anticoagulant substances. Then, a phenotype-anchored hierarchical strategy (the formula, the medicinal materials, and the representative compounds) was developed to reveal active substances, especially synergy. Meanwhile, phenotype-based topological network analysis was employed to delineate the pivotal targets. Dynamic blood flow imaging analysis in zebrafish was used to evaluate the effect of active substances in vivo. This approach enables rapid identification of active substances by hierarchically eliminating interference from inactive components, uncovers potential synergistic effects, and accelerates target identification by focusing on phenotype-relevant protein networks. Pentagalloylglucose, (+)-catechin, senkyunolide A, and lithospermic acid were considered as the anticoagulant substances of GXJF. Notably, synergy between hydroxysafflor yellow A and anhydrosafflor yellow B were discovered. Topological network analysis and enzyme activity assays suggested that they exert anticoagulant effects by inhibiting coagulation factors Xa and Ⅱa. These findings provide support for the clinical application of GXJF and establish a foundation for its quality control.

Sulfonamides (SNs) are a well-known class of antibiotics that have been explored in many areas of medicinal chemistry. Their broad spectrum of biological and medicinal properties, which includes antibacterial, anticancer, antifungal, anti-inflammatory, and enzyme inhibitory activities, has sustained continuous scientific interest. This review offers a thorough overview of the biological activities of SNs and their derivatives, with particular emphasis on their antibacterial and anticancer effects, as well as their role as carbonic anhydrase inhibitors. Additionally, we summarize some structure–activity relationship (SAR) studies that clarify how different substituents modulate potency and selectivity. By integrating insights from recent literature, this work, which is divided into five categories (antibacterial activity, anticancer activity, carbonic anhydrase inhibitory activity, and toxicity), highlights the pharmacological relevance of SNs, their structural diversity, and their continuing potential as scaffolds for creating new antibiotics.