Carboxamide derivatives are a promising class of compounds in anticancer drug discovery, owing to their ability to interact with multiple oncogenic targets and their favorable pharmacological profiles. In this study, we report the design, synthesis, and biological evaluation of a series of N-substituted 1H-indole-2-carboxamides as potential anticancer agents. The synthesized compounds were assessed for antiproliferative activity using the MTT assay against MCF-7 (breast cancer), K-562 (leukemia), and HCT-116 (colon cancer) cell lines, with normal human dermal fibroblasts included as a non-cancerous control. Several compounds demonstrated notable cytotoxicity and selectivity. Compounds 12, 14, and 4 exhibited potent activity against K-562 cells, with IC₅₀ values of 0.33 µM, 0.61 µM, and 0.61 µM, respectively. Compound 10 showed the most significant activity against HCT-116 cells (IC₅₀ = 1.01 µM) with a high selectivity index (SI = 99.4). Moderate cytotoxicity was observed against MCF-7 cells. To elucidate the mechanism of action, molecular docking and induced-fit docking studies were conducted against key cancer-related targets, including topoisomerase–DNA (PDB ID: 5ZRF), PI3Kα (4L23), and EGFR (3W32), revealing favorable binding interactions. Additionally, principal component analysis of molecular descriptors indicated that the compounds possess promising drug-like and lead-like properties, particularly compound 10. Overall, this study highlights N-substituted indole-2-carboxamides as promising scaffolds for further optimization. The integration of synthetic chemistry, biological assays, and computational modeling provides a robust foundation for the continued development of these compounds as potential anticancer agents.

Background/Objectives: Acne vulgaris is a chronic skin infection characterized by high sebum secretion, keratosis around hair follicles, inflammation, and imbalance in androgen levels. Acne vulgaris causes permanent scars or skin pigmentation in cases of improper treatment. Oral or topical isotretinoin, contraceptives, and antibiotics are used to treat acne. Minocycline is one of the widely used tetracyclines for this purpose; it inhibits the synthesis of proteins in bacterial ribosomes. Commonly, minocycline is prescribed daily for several months for acne vulgaris. Systemic minocycline is highly distributed into body fluids, and it is associated with several side effects and antibiotic resistance. Additionally, minocycline is highly metabolized in the liver, leading to reduced bioavailability upon systemic delivery. This study aims to develop and characterize minocycline nanocrystals for targeted skin delivery and evaluate their antimicrobial efficacy in treating acne vulgaris. Methods: Minocycline nanocrystals were synthesized using milling or solvent evaporation techniques. Nanocrystals were characterized in terms of particle size, particle distribution index (PDI), zeta potential, and morphology. The antibacterial efficacy against Propionibacterium acne, Staphylococcus aureus, and Staphylococcus epidermidis was evaluated using a minimum inhibitory concentration assay (MIC) and agar well diffusion test in comparison to coarse minocycline. Results: Minocycline nanocrystals had a particle size of 147.4 ± 7.8 nm and 0.27 ± 0.017 of PDI. The nanocrystals exhibited a loading efficiency of 86.19 ± 16.7%. Antimicrobial testing showed no significant difference in activity between minocycline and its nanoparticle formulation. In terms of skin deposition, the nanocrystals were able to deliver minocycline topically to rat skin significantly more than free minocycline. The nanocrystal solution deposited 554.56 ± 24.13 μg of minocycline into rat skin, whereas free minocycline solution deposited 373.99 ± 23.32 μg. Conclusions: Minocycline nanocrystals represent a promising strategy for targeted skin delivery in the treatment of acne vulgaris, potentially reducing systemic side effects and antibiotic resistance and improving patient outcomes.

Acne is a multifactorial skin condition characterized by an infection in the pilosebaceous units in the skin. Patients with acne suffer from comedones, papules, pustules and nodules or cysts in severe cases. These clinical features might cause disfigurmentation, depression, anxiety and significantly impact the quality of life of patients. Systemic and continuous exposure of antibiotics put patients at risk of developing systemic toxicity, bacterial resistance and gut dysbiosis. Microneedles offer an innovative approach of providing targeted topical delivery of minocycline while insuring efficient permeation through skin layers. Methods: minocycline microneedles were formulated using casting method and characterized for insertion ability, mechanical strength, drug content, antibacterial activities, deposition and dissolution behavior using ex vivo full-thickness rat skin. Results: Insertion tests confirmed effective skin penetration and mechanical integrity with only 9.5% height reduction. Drug content was 673.06 ± 5.34 µg/array. Dissolution occurred within 2 min in skin, indicating user-friendly wear time. Ex vivo Franz diffusion studies showed 26% of the drug deposited into the skin, significantly higher (p = 0.0068) than the 18.3% that permeated through it. Antibacterial testing revealed strong activity against S. aureus, S. epidermidis, and C. acnes, with MIC values < 0.146 µg/mL and MBC values ranging from 9.375–18.75 µg/mL. Conclusions: The result of this research demonstrate that minocycline microneedles effectively deliver minocycline into the skin highlighting their potential as a safer and more efficient alternative for acne therapy.

Background/Objectives: Hydrogels infused with silver nanoparticles (AgNPs) are widely used for their antibacterial properties, yet their stability, specifically upon contact with solid growth media (agar), remains poorly explored. This study compared two hydrogel matrices, anionic Carbopol 934 and non-ionic Pluronic F127, incorporating AgNPs of three different sizes. The evaluation focused on colloidal stability and antibacterial efficacy against Gram-positive and Gram-negative bacteria. Methods: In this study AgNPs (~20, ~55, and ~65 nm) were synthesised via a wet-chemical method and characterised by UV–visible spectroscopy, dynamic light scattering (DLS), and transmission electron microscopy (TEM). AgNPs were incorporated into Carbopol 934 and Pluronic F127 hydrogel matrices. Colloidal stability was monitored over four months of storage and upon contact with tryptic soy agar (TSA). Antibacterial activity was assessed using agar diffusion assays. Results: Showed that both hydrogel systems maintained AgNP stability during storage, comparable to aqueous suspensions. However, upon contact with TSA, aggregation of Carbopol–AgNP hydrogels occurred, whereas Pluronic–AgNP hydrogels remained stable. In antibacterial assays, both hydrogels produced larger zones of inhibition (ZOI) than AgNP suspensions against Gram-negative bacteria (E. coli, P. aeruginosa), with Carbopol–AgNP hydrogels demonstrating superior efficacy in an inverse size-dependent manner. Against Gram-positive bacteria (S. aureus, S. epidermidis), Pluronic–AgNP hydrogels initially showed larger ZOIs due to the polymer’s intrinsic antibacterial activity. However, after correcting for this baseline, Carbopol–AgNP hydrogels exhibited superior net efficacy, with S. epidermidis showing greater susceptibility than S. aureus. Conclusions: While both Carbopol 934 and Pluronic F127 stabilise AgNPs during storage, the matrix type significantly influences behaviour at the biological interface. Carbopol–AgNP hydrogels aggregate upon contact with solid agar yet deliver superior, size-dependent antibacterial activity compared to the stable but less potent Pluronic systems.

Acne is a multifactorial skin condition characterized by an infection in the pilosebaceous units in the skin. Patients with acne suffer from comedones, papules, pustules and nodules or cysts in severe cases. These clinical features might cause disfigurmentation, depression, anxiety and significantly impact the quality of life of patients. Systemic and continuous exposure of antibiotics put patients at risk of developing systemic toxicity, bacterial resistance and gut dysbiosis. Microneedles offer an innovative approach of providing targeted topical delivery of minocycline while insuring efficient permeation through skin layers. Methods: minocycline microneedles were formulated using casting method and characterized for insertion ability, mechanical strength, drug content, antibacterial activities, deposition and dissolution behavior using ex vivo full-thickness rat skin. Results: Insertion tests confirmed effective skin penetration and mechanical integrity with only 9.5% height reduction. Drug content was 673.06 ± 5.34 µg/array. Dissolution occurred within 2 minutes in skin, indicating user-friendly wear time. Ex vivo Franz diffusion studies showed 26% of the drug deposited into the skin, significantly higher (p = 0.0068) than the 18.3% that permeated through it. Antibacterial testing revealed strong activity against S. aureus, S. epidermidis, and C. acnes, with MIC values <0.146 µg/mL and MBC values ranging from 9.375–18.75 µg/mL. Conclusion: The result of this research demonstrate that minocycline microneedles effectively deliver minocycline into the skin highlighting their potential as a safer and more efficient alternative for acne therapy.

The increasing prevalence of multidrug-resistant (MDR) pathogens necessitates the discovery of novel antibacterial agents. In this study, culturable soil bacteria from the Dead Sea region (Jordan) were isolated and the antibacterial activity of their extracellular metabolites were evaluated. Twenty-one isolates were screened using a perpendicular-streak primary assay; three stable producers (GH-15, GH-20, GH-21) were prioritized. Cell-free supernatants were extracted with n-hexane and ethyl acetate, tested using agar well diffusion, and profiled using thin-layer chromatography (TLC) coupled with bioautography (GH-15). Minimum inhibitory concentration (MIC) and minimum bactericidal concentration (MBC) were determined by broth microdilution against Bacillus subtilis ATCC 11774, B. cereus ATCC 10876, Staphylococcus aureus ATCC 29213, Escherichia coli ATCC 25922, Pseudomonas aeruginosa ATCC 27853, and Proteus mirabilis ATCC 29906. The ethyl acetate extract of GH-15 showed the lowest MIC against E. coli (0.073 mg/mL). The MIC values were equal to MBC for several strains, indicating bactericidal activity. For GH-15 hexane extract, the lowest MIC was 2.625 mg/mL (E. coli and B. cereus), and the lowest MBC was 5.25 mg/mL (E. coli and B. cereus). Dead Sea soils yielded bacterial isolates with broad antibacterial activity; solvent-dependent activity and TLC-bioautography suggested multiple bioactive metabolites, supporting further purification and chemical identification.