Indole derivatives have become an important class of compounds in medicinal chemistry, recognized for their wide-ranging biological activities and therapeutic potential. This review provides a comprehensive overview of recent advances in the evaluation of indole-based compounds in the last five years, highlighting their roles in cancer treatment, infectious disease management, anti-inflammatory therapies, metabolic disorder interventions, and neurodegenerative disease management. Indole derivatives have shown significant efficacy in targeting diverse biological pathways, making them valuable scaffolds in designing new drugs. Notably, these compounds have demonstrated the ability to combat drug-resistant cancer cells and pathogens, a significant breakthrough in the field, and offer promising therapeutic options for chronic diseases such as diabetes and hypertension. By summarizing recent key findings and exploring the underlying biological mechanisms, this review underscores the potential of indole derivatives in addressing major healthcare challenges, thereby instilling hope and optimism in the field of modern medicine.

A series of novel thiazole-based chalcones were evaluated for their anticancer activity as potential tubulin polymerization inhibitors. In vitro anticancer screening for the thiazole derivatives 2a–2p exhibited broad-spectrum antitumor activity against various cancer cell lines particularly Ovar-3 and MDA-MB-468 cells with a GI₅₀ range from 1.55 to 2.95 μΜ, respectively. Compound 2e demonstrated significant inhibition of tubulin polymerization, with an IC₅₀ value of 7.78 μM compared to Combretastatin-A4 (CA-4), with an IC₅₀ value of 4.93 μM. Molecular docking studies of compounds 2e, 2g, and 2h into tubulin further supported these findings, revealing that they bind effectively to the colchicine binding site, mirroring key interactions exhibited by CA-4. Computational predictions suggested favorable oral bioavailability and drug-likeness for these compounds, highlighting their potential for further development as chemotherapeutic agents.

Ciprofloxacin, a widely used second-generation fluoroquinolone for treating bacterial infections, has recently shown notable anticancer properties. This review explores progress in developing ciprofloxacin derivatives with anticancer properties, emphasizing key structural changes that improve their therapeutic effectiveness by modifying the basic group at position 7, the carboxylic acid group at position 3, or both. It further investigates the mechanisms by which these derivatives fight cancer, such as inducing apoptosis, arresting the cell cycle, inhibiting topoisomerase I and II, preventing tubulin polymerization, suppressing interleukin 6, blocking thymidine phosphorylase, inhibiting multidrug resistance proteins, and hindering angiogenesis. Additionally, it outlines their future directions, such as enhancing their efficacy, selectivity, and investigating potential synergy with other chemotherapeutic agents, offering a promising avenue for developing new therapies for cancer.

This study investigated lacosamide (LCM), a third-generation antiepileptic drug, as a potential gonadoprotective agent against cyclophosphamide (CP)-induced testicular injury. The research addressed the critical need for safer antiepileptic alternatives in cancer patients requiring concurrent chemotherapy and seizure control. Male Wistar rats underwent comprehensive biochemical and histopathological analyses including Western blot, quantitative reverse transcription polymerase chain reaction (qRT-PCR), immunohistochemistry, steroidogenic enzyme activity assessments, sexual hormone measurements, sperm quality evaluations, and molecular docking studies to evaluate LCM's protective mechanisms against CP-induced testicular damage. CP administration significantly elevated oxidative stress markers, pro-inflammatory mediators (Nuclear factor kappa B [NF- κ B], Tumor necrosis factor-α [TNF-α], Interleukin-6 [IL-6], Interleukin-1β [IL-1β]), and apoptotic signaling (Bcl-2-associated x protein [Bax], caspase-3), while activating regulatory proteins c-jun N-terminal kinase 1 (JNK1) and Signal transducer and activator of transcription 3 (STAT-3) (identified as novel markers in CP-induced testicular injury). CP suppressed antioxidant defenses, steroidogenic factors (steroidogenic acute regulatory protein [StAR], 3β-hydroxysteroid dehydrogenase [3β-HSD], 17β-hydroxysteroid dehydrogenase [17β-HSD]), Heme oxygenase 1 (HO-1) expression, and androgen receptor (AR) functionality, resulting in decreased testosterone, gonadotropin levels, and compromised spermatogenesis. LCM treatment effectively mitigated these deleterious effects through multi-target protective mechanisms including c-jun N-terminal kinase 1(JNK1)-mediated apoptosis inhibition, HO-1 upregulation, IL-6/ signal transducer and activator of transcription 3 (STAT-3) signaling suppression, prevention of p-JNK1/STAT-3 crosstalk, and AR preservation. This study establishes LCM's multi-target protective efficacy, supporting its potential as a safer antiepileptic alternative providing dual benefits of seizure control and reproductive preservation during chemotherapy. Graphical Abstract