Gene-deficient mouse model established by CRISPR/Cas9 system reveals 15 reproductive organ-enriched genes dispensable for male fertility.

Since the advent of gene-targeting technology in embryonic stem cells, mice have become a primary model organism for investigating human gene function due to the striking genomic similarities between the two species. With the introduction of the CRISPR/Cas9 system for genome editing in mice, the pace of loss-of-function analysis has accelerated significantly. This has led to the identification of numerous genes that play crucial roles in male reproductive processes, including meiosis, chromatin condensation, flagellum formation in the testis, sperm maturation in the epididymis, and fertilization in the oviduct. Despite the advancements, the functions of many genes, particularly those enriched in male reproductive tissues, remain largely unknown. In our study, we focused on 15 genes and generated 13 gene-deficient mice [4933411K16Rik, Adam triple (Adam20, Adam25, and Adam39), BC048671, Cfap68, Gm4846, Gm4984, Gm13570, Nt5c1b, Ppp1r42, Saxo4, Sh3d21, Spz1, and Tektl1] to elucidate their roles in male fertility. Surprisingly, all 13 gene-deficient mice exhibited normal fertility in natural breeding experiments, indicating that these genes are not essential for male fertility. These findings have important implications as they may help prevent other research laboratories from duplicating efforts to generate knockout mice for genes that do not demonstrate an apparent phenotype related to male fertility. By shedding light on the dispensability of these genes, our study contributes to a more efficient allocation of research resources in the exploration of male reproductive biology.

Investigation of Urinary Metabolites of Organophosphate Esters in Hanoi, Vietnam: Assessment Exposure and Estimated Daily Intake.

In recent years, organophosphate esters (OPEs) have become one of the most common additives in various consumer products worldwide, therefore the exposure and impact of OPEs on human health are drawing a lot of attention. In this study, three metabolites of OPEs including bis(1,3-dichloro-2-propyl) phosphate (BDCIPP), diphenyl phosphate (DPhP) and diethyl phosphate (DEP) were investigated in first-morning void urine samples taken from a population (age range: 3-76 years old) in Hanoi, Vietnam. The most dominant urinary OPE metabolite was DEP with the geometric mean of specific gravity adjust (SG-adjusted) concentration were 1960 ng mL-1 and detected frequency (DF) of 98%. Followed by DPhP (8.01 ng mL-1, DF: 100%) and BDCIPP (2.18 ng mL-1, DF: 51%). The results indicated that gender and age might have associations with the OPE metabolites variation in urine samples. The levels of OPE metabolites in urine samples from females were slightly higher than in males. An increase in age seems to have an association with a decrease in DPhP levels in urine. Exposure doses of parent OPEs were evaluated from the unadjusted urinary concentration of corresponding OPE metabolite. The estimated exposure doses of triethyl phosphate (TEP) (mean: 534,000 ng kg-1 d-1) were significantly higher than its corresponding reference dose, suggesting the high potential risk from the current exposure doses of TEP to human health. The results of this work provided the initial information on the occurrence of three OPE metabolites in urine from Hanoi, Vietnam and estimated exposure dose of corresponding parent OPEs.

Improved synthesis, molecular modeling and anti-inflammatory activity of new fluorinated dihydrofurano-naphthoquinone compounds.

A series of new fluorinated dihydrofurano-napthoquinone compounds were sucessfully synthesized in good yields using microwave-assisted multi-component reactions of 2-hydroxy-1,4-naphthoquinone, fluorinated aromatic aldehydes, and pyridinium bromide. The products were fully characterized using spectroscopic techniques and evaluated for their anti-inflammatory activity using lipopolysaccharide (LPS)-stimulated RAW264.7 macrophage cells. Among 12 new compounds, compounds 8b, 8d, and 8e showed high potent NO inhibitory activity in lipopolysaccharide (LPS)-stimulated RAW264.7 macrophage cells with IC50 values ranging from 1.54 to 3.92 µM. The levels of pro-inflammatory cytokines IL-1ß and IL-6 in LPS-stimulated RAW264.7 macrophages were remarkably decreased after the application of 8b, 8d, 8e and 8k. Molecular docking simulations revealed structure-activity relationships of 8b, 8d, and 8e toward NO synthase, cyclooxygenase (COX-2 over COX-1), and prostaglandin E synthase-1 (mPGES-1). Further physicochemical and pharmacokinetic computations also demonstrated the drug-like characteristics of synthesized compounds. These findings demonstrated the importance of fluorinated dihydrofurano-napthoquinone moieties in the development of potential anti-inflammatory agents.

Pretibial myxedema in Grave's disease: A case report and treatment review of the literature.

Key Clinical Message: Pretibial myxedema is a rare skin lesion in Grave's disease, which required topical glucocorticoid administration in long-term treatment. The patient's lesion has shrunk and become flatter than before treatment. Abstract: We present a case of biopsy-verified pretibial myxedema in a 70-year-old male patient with diagnosed hyperthyroidism and no prior history of Graves' disease. Topical corticosteroid and antithyroid drug administration led to successful resolution of the skin lesions. This case emphasizes the importance of considering pretibial myxedema even in atypical presentations of Graves' disease and underscores the value of prompt treatment.

Ozanimod Therapy in Patients With COVID-19 Requiring Oxygen Support: A Randomized Open-Label Pilot Trial.

BACKGROUND: Sphingosine-1-phosphate receptor ligands (SRLs) dampen immunopathologic damages in models of viral pneumonia. RESEARCH QUESTION: Is it feasible to administer an SRL therapy, here ozanimod (OZA), to acutely ill patients infected with SARS-CoV-2? STUDY DESIGN AND METHODS: The prospective randomized open-label COVID-19 Ozanimod Intervention (COZI) pilot trial was conducted in three Canadian hospitals. Patients admitted for COVID-19 requiring oxygen were eligible. Randomization was stratified for risk factors of poor outcome and oxygen needs at inclusion. Participants were allocated to standard of care or to standard of care plus OZA. OZA (oral, once daily, incremental dosage) was administered for a maximum of 14 days. Primary end point investigated for size effect and variance over time was the assessment of safety and efficacy, evaluated by the daily score on the World Health Organization-adapted six-point ordinal scale for clinical improvement analyzed under the intention-to-treat principle. RESULTS: Twenty-three patients were randomized to the standard of care arm, and 20 were randomized to the OZA arm from September 2020 to February 2022. Evaluation of efficacy showed nonsignificant reductions of median (interquartile range) duration of respiratory support (6 [3-10] vs 9 [4-12] days; P = .34), median duration of hospitalization (9 [6-12] vs 10 [6-18] days; P = .20), and median time to clinical improvement (4 [3-7] vs 7 [3-11] days; P = .12) for OZA compared with standard of care, respectively. Heart rate was significantly lower with OZA (65 [ 63-67] vs 71 [69-72] beats/min; P < .0001). However, QT and PR intervals were not affected. No severe adverse drug reaction was reported. INTERPRETATION: To our knowledge, SRL utility in severe pneumonia has never been tested in patients. This study shows for the first time that this new pharmacologic agent may safely be administered to patients hospitalized for viral pneumonia, with potential clinical benefits. Bradycardia was frequent but well tolerated. CLINICAL TRIAL REGISTRATION: ClinicalTrials.gov; No.: NCT04405102; URL: www. CLINICALTRIALS: gov.

Synthesis, in vitro Α-Glucosidase, and acetylcholinesterase inhibitory activities of novel Indol-Fused Pyrano[2,3-D]Pyrimidine compounds.

In this study, new indol-fused pyrano[2,3-d]pyrimidines were designed and synthesized. These products were obtained in moderate to good yields and their structures were assigned by NMR, MS, and IR analysis. Afterwards, the biological important of the products was highlighted by evaluating in vitro for α-glucosidase inhibitory activity as well as acetylcholinesterase (AChE) inhibitory activity. Eleven products revealed substantial inhibitory activity against α-glucosidase enzyme, among which, two most potent products 11d,e were approximately 93-fold more potent than acarbose as a standard antidiabetic drug. Besides that, product 11k exhibited good AChE inhibition. The substituents on the 5-phenyl ring, attached to the pyran ring, played a critical role in inhibitory activities. The biological potencies have provided an opportunity to further investigations of indol-fused pyrano[2,3-d]pyrimidines as potential anti-diabetic agents.

Toxicological effects of diclofenac on signal crayfish (Pacifastacus leniusculus) as related to weakly acidic and basic water pH.

The widespread use and continuous discharge of pharmaceuticals to environmental waters can lead to potential toxicity to aquatic biota. Pharmaceuticals and their metabolites are often complex organic and environmentally persistent compounds that are bioactive at low doses. This study aimed to investigate the effects of diclofenac (DCF) on the antioxidant defence system and neurotoxicity biomarkers in signal crayfish (Pacifastacus leniusculus) under weakly acidic and basic conditions. Crayfish were exposed to 200 µg/L of DCF at pH 6 and 8 for 96 h and subsequently underwent the depuration phase for 96 h. Gills, hepatopancreas, and muscle were sampled after the exposure and depuration phases to assess the toxicological biomarker responses of DCF in crayfish by evaluating lipid peroxidation (LPO) levels, activities of antioxidant enzymes and acetylcholinesterase. After the exposure phase, the hemolymph DCF concentration was detected one order higher at pH 6 than at pH 8. The DCF was subsequently fully eliminated from the hemolymph during the depuration phase. Our results showed that DCF caused alteration in the activities of six of the seven tested biomarkers in at least one crayfish tissue. Although exposure to DCF caused imbalances in the detoxification system on multiple tissue levels, it was regenerated to a balanced state after the depuration phase. Integrated biomarker response (IBRv2) showed that the highest toxicological response to DCF exposure was elicited in the gills, whereas the hepatopancreas was the highest-responding tissue after the depuration phase. Exposure to DCF at pH 6 caused higher toxicological effects than at pH 8; however, crayfish antioxidant mechanisms recovered more quickly at pH 6 than at pH 8 after the depuration phase. Our results showed that water pH influenced the toxicological effects of DCF, an ionisable compound in crayfish.

A fatal eosinophilic granulomatosis with polyangiitis case presenting intracerebral hemorrhage and thrombocytopenia.

We report the case of a patient with eosinophilic granulomatosis with polyangiitis and unexplained thrombocytopenia that culminated in a fatal intracerebral hemorrhage. Because vessel damage associated with thrombocytopenia could be the leading cause of fatal hemorrhage, more urgent treatment of thrombocytopenia should be performed in such cases.

RNAi-mediated rheostat for dynamic control of AAV-delivered transgenes.

Adeno-associated virus (AAV)-based gene therapy could be facilitated by the development of molecular switches to control the magnitude and timing of expression of therapeutic transgenes. RNA interference (RNAi)-based approaches hold unique potential as a clinically proven modality to pharmacologically regulate AAV gene dosage in a sequence-specific manner. We present a generalizable RNAi-based rheostat wherein hepatocyte-directed AAV transgene expression is silenced using the clinically validated modality of chemically modified small interfering RNA (siRNA) conjugates or vectorized co-expression of short hairpin RNA (shRNA). For transgene induction, we employ REVERSIR technology, a synthetic high-affinity oligonucleotide complementary to the siRNA or shRNA guide strand to reverse RNAi activity and rapidly recover transgene expression. For potential clinical development, we report potent and specific siRNA sequences that may allow selective regulation of transgenes while minimizing unintended off-target effects. Our results establish a conceptual framework for RNAi-based regulatory switches with potential for infrequent dosing in clinical settings to dynamically modulate expression of virally-delivered gene therapies.

Occurrence and ecological risk assessment of organophosphate esters in surface water from rivers and lakes in urban Hanoi, Vietnam.

In this study, an investigation on the pollution status, distribution, and ecological risk to the aquatic organisms of six organophosphate tri-esters (tri-OPEs) and two organophosphate tri-esters (di-OPEs) in surface water in urban Hanoi, Vietnam were conducted. In 37 surveyed water samples (6 rivers and 17 lakes), all eight targeted OPEs were discovered with a detection frequency (DF) of 41-100% and the concentration varied largely from below the method detection limit (

A Fast and Easy Method to Co-extract DNA and RNA from an Environmental Microbial Sample.

We herein propose a fast and easy DNA and RNA co-extraction method for environmental microbial samples. It combines bead beating and phenol-chloroform phase separation followed by the separation and purification of DNA and RNA using the Qiagen AllPrep DNA/RNA mini kit. With a handling time of ~3 h, our method simultaneously extracted high-quality DNA (peak size >10-15| |kb) and RNA (RNA integrity number >6) from lake bacterioplankton filtered samples. The method is also applicable to low-biomass samples (expected DNA or RNA yield <50| |ng) and eukaryotic microbial samples, providing an easy option for more versatile eco-genomic applications.

Metabolically Stable Anomeric Linkages Containing GalNAc-siRNA Conjugates: An Interplay among ASGPR, Glycosidase, and RISC Pathways.

Conjugation of synthetic triantennary N-acetyl-d-galactosamine (GalNAc) to small interfering RNA (siRNA) mediates binding to the asialoglycoprotein receptor (ASGPR) on the surface of hepatocytes, facilitating liver-specific uptake and siRNA-mediated gene silencing. The natural ß-glycosidic bond of the GalNAc ligand is rapidly cleaved by glycosidases in vivo. Novel GalNAc ligands with S-, and C-glycosides with both α- and ß-anomeric linkages, N-glycosides with ß-anomeric linkage, and the O-glycoside with α-anomeric linkage were synthesized and conjugated to siRNA either on-column during siRNA synthesis or through a high-throughput, post-synthetic method. Unlike natural GalNAc, modified ligands were resistant to glycosidase activity. The siRNAs conjugated to newly designed ligands had similar affinities for ASGPR and similar silencing activity in mice as the parent GalNAc-siRNA conjugate. These data suggest that other factors, such as protein-nucleic acid interactions and loading of the antisense strand into the RNA-induced silencing complex (RISC), are more critical to the duration of action than the stereochemistry and stability of the anomeric linkage between the GalNAc moiety of the ligand conjugated to the sense strand of the siRNA.

Sequential Targeting of Retinoblastoma and DNA Synthesis Pathways Is a Therapeutic Strategy for Sarcomas That Can Be Monitored in Real Time.

Treatment strategies with a strong scientific rationale based on specific biomarkers are needed to improve outcomes in patients with advanced sarcomas. Suppression of cell-cycle progression through reactivation of the tumor suppressor retinoblastoma (Rb) using CDK4/6 inhibitors is a potential avenue for novel targeted therapies in sarcomas that harbor intact Rb signaling. Here, we evaluated combination treatment strategies (sequential and concomitant) with the CDK4/6 inhibitor abemacicib to identify optimal combination strategies. Expression of Rb was examined in 1,043 sarcoma tumor specimens, and 50% were found to be Rb-positive. Using in vitro and in vivo models, an effective two-step sequential combination strategy was developed. Abemaciclib was used first to prime Rb-positive sarcoma cells to reversibly arrest in G1 phase. Upon drug removal, cells synchronously traversed to S phase, where a second treatment with S-phase targeted agents (gemcitabine or Wee1 kinase inhibitor) mediated a synergistic response by inducing DNA damage. The response to treatment could be noninvasively monitored using real-time positron emission tomography imaging and serum thymidine kinase activity. Collectively, these results show that a novel, sequential treatment strategy with a CDK4/6 inhibitor followed by a DNA-damaging agent was effective, resulting in synergistic tumor cell killing. This approach can be readily translated into a clinical trial with noninvasive functional imaging and serum biomarkers as indicators of response and cell cycling. SIGNIFICANCE: An innovative sequential therapeutic strategy targeting Rb, followed by treatment with agents that perturb DNA synthesis pathways, results in synergistic killing of Rb-positive sarcomas that can be noninvasively monitored.

Radiofrequency versus Ethanol Ablation for Single-Session Treatment of Benign Cystic Thyroid Nodules: A Short-Term Retrospective Study.

Objective: This study aims to compare 1-month's efficacy and safety of single-session ethanol ablation and radiofrequency ablation for treating both purely cystic nodules and predominantly cystic thyroid nodules. Materials and methods: This short-term retrospective study was approved by the Ethics Committee of the Institutional Review Board of Danang Family hospital, and written informed consent for procedures was obtained for all patients. Thirty-nine patients who presented with cystic thyroid nodules and met inclusion criteria were extracted from the computerized medical records. The internal fluid of cystic thyroid nodules was aspirated as much as possible. Ethanol ablation was performed using 18-gauge needles with 99.5% ethanol, and RFA used a cooled-electrode RFA system and 18-gauge internally cooled electrodes via the trans-isthmic approach, moving-shot technique. Nodule volume, therapeutic success rate, the largest diameter, thyroid function tests, and complications were evaluated and compared before and after treatment in each group. Results: Among 39 patients, 17 patients were undergone EA (mean age of 47.35 years; the proportion of female of 76.5%; purely thyroid cyst percentage of 41.4%) and 22 patients were undergone RFA (mean age of 46.63 years; the proportion of female of 86.4%; purely thyroid cyst percentage of 54.5%). Both treatment techniques showed a significant reduction of the largest diameter and nodule volume (p<0.05) without complications. RFA reduced nodule volume and the largest nodule size greater than EA treatment at 1-month post-ablation (p<0.05). In addition, the therapeutic success rate in the RFA group was higher than in the EA group. Conclusion: Both RFA and EA treatment with single-session confirm the efficacy and safety for cystic thyroid nodules at 1-month follow-up, RFA reduced greater in nodule volume and the largest nodule size than the EA treatment. Thus, the therapeutic success rate in the RFA group was higher than in the EA group.

Low-molecular-weight cyclin E deregulates DNA replication and damage repair to promote genomic instability in breast cancer.

Low-molecular-weight cyclin E (LMW-E) is an N-terminus deleted (40 amino acid) form of cyclin E detected in breast cancer, but not in normal cells or tissues. LMW-E overexpression predicts poor survival in breast cancer patients independent of tumor proliferation rate, but the oncogenic mechanism of LMW-E and its unique function(s) independent of full-length cyclin E (FL-cycE) remain unclear. In the current study, we found LMW-E was associated with genomic instability in early-stage breast tumors (n = 725) and promoted genomic instability in human mammary epithelial cells (hMECs). Mechanistically, FL-cycE overexpression inhibited the proliferation of hMECs by replication stress and DNA damage accumulation, but LMW-E facilitated replication stress tolerance by upregulating DNA replication and damage repair. Specifically, LMW-E interacted with chromatin and upregulated the loading of minichromosome maintenance complex proteins (MCMs) in a CDC6 dependent manner and promoted DNA repair in a RAD51- and C17orf53-dependent manner. Targeting the ATR-CHK1-RAD51 pathway with ATR inhibitor (ceralasertib), CHK1 inhibitor (rabusertib), or RAD51 inhibitor (B02) significantly decreased the viability of LMW-E-overexpressing hMECs and breast cancer cells. Collectively, our findings delineate a novel role for LMW-E in tumorigenesis mediated by replication stress tolerance and genomic instability, providing novel therapeutic strategies for LMW-E-overexpressing breast cancers.

Fabrication of binary g-C3N4/UU-200 composites with enhanced visible-light-driven photocatalytic performance toward organic pollutant eliminations.

In this study, g-C3N4/UU-200 heterojunction photocatalysts displaying superior photocatalytic activity for organic pollutant elimination under white LED light irradiation were fabricated via an in situ solvothermal method. The successful construction of a heterojunction between g-C3N4 and UU-200 was evidenced by X-ray diffraction, Fourier transform infrared spectroscopy, X-ray photoelectron spectroscopy, scanning electron microscopy, and transmission electron microscopy. The improved photocatalytic degradation of rhodamine B (RhB) and tetracycline hydrochloride (TCH) over g-C3N4/UU-200 compared with that over the individual components can be attributed to the anchoring of the g-C3N4 layered structure on the UU-200 surface promoting the decrease of the bandgap of UU-200, as confirmed by ultraviolet-visible diffuse reflectance spectroscopy, and to the light-induced charge separation efficiency stemming from a suitable heterojunction structure, which was revealed by photoluminescence spectroscopy and electrochemical analyses. Specifically, the 40% g-C3N4/UU-200 composite showed the highest photocatalytic activity toward the degradation of RhB (97.5%) within 90 min and TCH (72.6%) within 180 min. Furthermore, this catalyst can be recycled four runs, which demonstrates the potential of the g-C3N4/UU-200 composite as an alternative visible-light-sensitive catalyst for organic pollutant elimination.

Synthesis, Biological Evaluation, and Molecular Modeling Studies of 1-Aryl-1H-pyrazole-Fused Curcumin Analogues as Anticancer Agents.

Addressing the growing burden of cancer and the shortcomings of chemotherapy in cancer treatment are the current research goals. Research to overcome the limitations of curcumin and to improve its anticancer activity via its heterocycle-fused monocarbonyl analogues (MACs) has immense potential. In this study, 32 asymmetric MACs fused with 1-aryl-1H-pyrazole (7a-10h) were synthesized and characterized to develop new curcumin analogues. Subsequently, via initial screening for cytotoxic activity, nine compounds exhibited potential growth inhibition against MDA-MB-231 (IC50 2.43-7.84 µM) and HepG2 (IC50 4.98-14.65 µM), in which seven compounds showing higher selectivities on two cancer cell lines than the noncancerous LLC-PK1 were selected for cell-free in vitro screening for effects on microtubule assembly activity. Among those, compounds 7d, 7h, and 10c showed effective inhibitions of microtubule assembly at 20.0 µM (40.76-52.03%), indicating that they could act as microtubule-destabilizing agents. From the screening results, three most potential compounds, 7d, 7h, and 10c, were selected for further evaluation of cellular effects on breast cancer MDA-MB-231 cells. The apoptosis-inducing study indicated that these three compounds could cause morphological changes at 1.0 µM and could enhance caspase-3 activity (1.33-1.57 times) at 10.0 µM in MDA-MB-231 cells, confirming their apoptosis-inducing activities. Additionally, in cell cycle analysis, compounds 7d and 7h at 2.5 µM and 10c at 5.0 µM also arrested MDA-MB-231 cells in the G2/M phase. Finally, the results from in silico studies revealed that the predicted absorption, distribution, metabolism, excretion, and the toxicity (ADMET) profile of the most potent MACs might have several advantages in addition to potential disadvantages, and compound 7h could bind into (ΔG -10.08 kcal·mol-1) and access wider space at the colchicine-binding site (CBS) than that of colchicine or nocodazole via molecular docking studies. In conclusion, our study serves as a basis for the design of promising synthetic compounds as anticancer agents in the future.

Integrated biomarker response in signal crayfish Pacifastacus leniusculus exposed to diphenhydramine.

Diphenhydramine (DPH) is a pharmaceutical with multiple modes of action, primarily designed as an antihistamine therapeutic drug. Among antihistamines, DPH is a significant contaminant in the environment, frequently detected in surface waters, sediments, and tissues of aquatic biota. In the present study, signal crayfish Pacifastacus leniusculus was used as a model organism because of their prominent ecological roles in freshwater ecosystems. The biochemical effects were investigated in crayfish exposed to the environmental (low: 2 µg L-1), ten times elevated (medium: 20 µg L-1), and the sublethal (high: 200 µg L-1) nominal concentrations of DPH in water for 96 h. Lipid peroxidation, antioxidant enzyme activities, and acetylcholinesterase activity were assessed as toxicological biomarkers in crayfish hepatopancreas, gills, and muscles. Low and medium DPH exposure caused imbalances only in glutathione-like enzyme activities. Integrated biomarker response showed the absolute DPH toxicity effects on all tested tissues under high exposure. This study identified that high, short-term DPH exposure induced oxidative stress in crayfish on multiple tissue levels, with the most considerable extent in muscles.

Microwave-Assisted Three-Component Synthesis of Novel N-Arylated-Dihydrobenzo[g]quinoline-5,10-Diones and Their Potential Cytotoxic Activity.

A convenient three-component synthetic approach was developed en route to new and significative N-arylated-dihydrobenzo[g]quinoline-5,10-diones using 2-hydroxy-1,4-naphthoquinone, a variety of aromatic aldehydes, and 4-(arylamino)furan-2(5H)-ones. A sequence of steps including Knoevenagel condensation, Michael addition, [1,3]-hydrogen shift, intramolecular cyclization and dehydration led to the formation of products. All the products were structurally characterized by spectroscopic techniques and assessed in terms of their cytotoxicity profile against four cancer cell lines (KB, HepG2, A549, and MCF7), and human embryonic kidney (Hek-293) cell lines.

Synthesis and biological activity, and molecular modelling studies of potent cytotoxic podophyllotoxin-naphthoquinone compounds.

A new approach for the synthesis of podophyllotoxin-naphthoquinone compounds using microwave-assisted three-component reactions is reported in this study. Novel podophyllotoxin-naphthoquinone derivatives with modification on ring E were synthesized. All the synthetic compounds were assessed in terms of their cytotoxicity profile against four cancer cell lines (KB, HepG2, A549, and MCF7), and noncancerous Hek-293 cell lines. Notably, treatment of SK-LU-1 cells with compounds 5a and 5b resulted in G2/M phase arrest of the cell cycle, caspase-3/7 activation, and apoptosis. Additionally, molecular docking studies were performed and showed important interaction of two compounds against residues in the colchicine-binding-site of tubulin as well. Taken together, compounds 5a and 5b were identified as potent anticancer agents.