Thymol, a natural monoterpene phenol is not only relevant clinically as an anti-microbial, anti-oxidant and anti-inflammatory agent but also holds the prospect as a natural template for pharmaceutical semi-synthesis of therapeutic agents. It is a major component of essential oils from many plants. Evidence abound linking overall bioactivity of thymol to its monoterpene nucleus, specifically, the hydroxyl (-OH) substituent on carbon number one (C1) on the monoterpene nucleus. Other studies have posited that the overall bioactivity of thymol is not substantially altered by chemical modification of - OH on the C1 of the monoterpene nucleus. In view of this, it is still unclear as to whether removal or modification of the -OH on C1 of the monoterpene nucleus relates generally or context-dependently to bioactivity of thymol. The present study investigated anti-bacterial effects of ester-and-ether substituted derivatives of thymol on S. aureus, P. aeruginosa and E. coli. twelve ester-and-ether substituted derivatives of thymol (6TM1s and 6TM2s) were synthesized and characterized by using HPLC, Mass spectrometry, and IR techniques. Anti-bacterial activity of the 12 thymol derivatives was evaluated using broth macrodilution and turbidimetric methods against pure clinical isolates (S. aureus, P. aeruginosa and E. coli). Standard anti-biotics used were Thymol Streptomycin and flucloxacillin, while DMSO was used as vehicle for thymol derivatives. MIC and MBC were determined. Thymol produced broad-spectrum growth inhibition on all isolates. At equimolar concentrations, thymol and reference drugs produced concentration-dependent growth inhibition against the isolates (Staphylococcus aureus, Pseudomonas aeruginosa and Escherichia coli) compared to DMSO. Although the growth inhibitory effects of the ester-and-ether derivatives of thymol was significant (P ≤ 0.05) compared to DMSO, it was however insignificant (P ≥ 0.05) compared to thymol and reference antibiotics. Comparatively, at equimolar concentrations, ester-substituted derivatives of thymol, particularly the branched chain derivative (TM1C) produced more effective growth inhibition on the isolates than the ether-substituted derivatives of thymol. Thymol was twice as potent (MIC and MBC, 500 μg/ml) than both ester-and-ether substituted derivatives of thymol (MIC and MBC, > 1000 μg/ml) on all the three clinical isolates. Increase in side chain bulkiness of -OH moiety on the monoterpene nucleus of thymol decreased growth inhibition on isolates. Thymol has demonstrated broad-spectrum anti-bacterial effects attributable to the hydroxyl moiety on C1 of the monoterpene nucleus. Structural modification of the hydroxyl moiety on C1 of the monoterpene nucleus of thymol with either ether-or-ester substitutions yielded no significant anti-bacterial effects.

Breast cancer is the second leading cause of cancer-related mortality among women globally with obesity being one risk factor. Obese breast cancer patients have at least a 30% increased risk of death from breast cancer compared to non-obese breast cancer patients because they present with larger tumors and generally have increased rates of metastasis. Moreover, obese breast cancer patients respond more poorly to treatment compared to non-obese patients, particularly pre-menopausal women diagnosed with triple negative breast cancer (TNBC). To help understand the molecular mechanisms underlying the increased metastasis associated with obesity, we previously established a three-dimensional culture system that permits the co-culture of adipocytes and TNBC cells in a manner that mimics an in vivo milieu. Using this system, we demonstrate that white adipose tissue from both lean and obese mice can induce a partial mesenchymal-to-epithelial transition (MET). Triple negative breast cancer cells adopt an epithelial morphology and have an increased expression of some epithelial markers, but they maintain the expression of mesenchymal markers, furnishing the breast cancer cells with hybrid properties that are associated with more aggressive tumors. Thus, these data suggest that adipose tissue has the potential to promote secondary tumor formation in lean and obese women. Further work is needed to determine if targeting the partial MET induced by adipose tissue could reduce metastasis.

Objective. This study aimed to determine whether the kinetics of sublethal damage recovery after x-ray irradiation, quantified as the repair half time ( T repair SLD ) derived from split-dose clonogenic survival, correlates with intrinsic radiosensitivity across four human cancer cell lines: HeLa (cervical), PC3 (prostate), and HCT116 and HT29 (colorectal). In addition, the study compared this survival-based indicator with molecular repair kinetics assessed through γH2AX and 53BP1 foci clearance. Approach. By using a phenomenological approach, we assessed sublethal damage recovery kinetics, aiming to determine whether this recovery rate could serve as a biomarker for cancer-specific intrinsic radiosensitivity. Cells were subjected to split-dose 4 Gy irradiation delivered in two fractions of 2 Gy across a 0 to 10 h inter-fraction interval range using a Multi-Rad x-ray irradiator with a peak tube voltage of 225 kV. The clonogenic assay was performed following split-dose irradiation of the experimental groups to assess cell survival. Colonies were fixed, stained, and counted ( ⩾ 50 cells/colony viable threshold) to calculate survival fractions (SFs) from the four independent experimental runs completed for each cell line. Unirradiated control cells were used to calculate plating efficiency. The measured SF as a function of inter-fraction time was fitted with the Lea–Catcheside modified linear-quadratic model with a half-life of sublethal damage repair, T repair SLD , as a free parameter. To compare this approach to molecular DNA repair kinetics, immunofluorescence-based ionizing radiation-induced foci (IRIF) clearance experiments were performed following single 2 Gy irradiation using the same x-ray source. γH2AX and 53BP1 foci were quantified from 0.5 to 24 h post-irradiation, and foci clearance half-lives ( T repair γ H 2 AX and T repair 53 BP 1 ) were determined by single-phase exponential decay fitting. Main results. For all measured cell lines, an increase in SF was observed with increasing inter-fraction time. The estimated T repair SLD varied across cell lines, from 1.07 ± 0.35 h in HT29, to 1.98 ± 0.94 h in HeLa, 2.00 ± 0.30 h in PC3, and 3.58 ± 1.45 h in HCT116, indicating different capacities for sublethal damage repair. A negative correlation was measured between T repair SLD and clonogenic survival at 2 Gy ( SF 2 Gy ) by performing orthogonal distance regression, with a slope of − 350 ± 50 min (p = 0.02). T repair γ H 2 AX and T repair 53 BP 1 ranged from 3 to 11 h, with HT29 showing the fastest foci resolution. However, these molecular repair kinetics times did not significantly correlate with SF 2 Gy (p > 0.05) or follow the same trend as T repair SLD across cell lines. For example, PC3 cells exhibited the slowest foci clearance, whereas HCT116 displayed the slowest T repair SLD , suggesting that IRIF-based measurements do not reliably reflect functional sublethal damage repair. Significance. Clonogenic survival assays capture the integrated biological outcome of radiation exposure, reflecting not only DNA damage recognition and repair but also downstream processes such as checkpoint activation, chromatin context, and long-term proliferative capacity. In contrast, molecular readouts like γH2AX and 53BP1 foci clearance, though rapid and widely used, may not fully account for defects in damage response pathways. The observed discrepancy between foci clearance kinetics and survival-based repair rates in this study highlights the limitations of foci quantification as a surrogate for radiosensitivity. These findings underscore the value of survival-based sublethal damage recovery measurements as functionally rich indicators of intrinsic radiosensitivity, which may inform future biomarker development or predictive modeling frameworks.