Compound B3 Research Articles

Novel Insecticidal Pyridylhydrazono Derivatives Identified via Scaffold Hopping and Conformation Regulation Strategies.

Insect transient receptor potential vanilloid (TRPV) channels are critical targets for insecticides. In this study, various scaffold-hopping strategies were employed in the rational design of pyridylhydrazono derivatives as potential insect TRPV channels modulators. Insecticidal bioassay demonstrated that the initial target compounds exhibited lower insecticidal activity compared to pymetrozine, with the optimal compound B3 exhibiting a mortality rate of 53.3 % against Aphis craccivora at 400 mg L-1. Conformation analysis indicated that the high energy barrier required for the transition from the lowest-energy conformation to the active conformation may be a key factor contributing to the reduced insecticidal activities of the target compounds. Further structural optimizations aimed at reducing this energy barrier through binding mode-based conformation regulation led to the identification of optimal target 4-(3'-pyridylhydrazono)pyrazol-5-one derivatives C1 and C2. These compounds exhibited reduced transition energy barriers and improved insecticidal activity, with moderate mortality rate of 66.3 % and 75.7 % against A. craccivora at 400 mg L-1, respectively. These findings provide valuable insights for future research on the discovery of insect TRPV modulators and have significant implications for the development of more effective agricultural insecticides.

Design, synthesis, evaluation and optimization of novel azole analogues as potent antifungal agents

In order to develop antifungal drugs, a series of novel azole analogues were designed and synthesized based on our previous work. Most of the target compounds had broad-spectrum antifungal activity, which showed excellent to moderate inhibitory activity against the tested strains, except A. fum 0504656. Among these, compounds B3, B7, B8, B11, B12 and E9 showed excellent activity against C. alb Y0109 and C. alb SC5314 (with the MIC80: 0.0156 ug/mL). In addition, compound B3 showed the best inhibitory activity against fluconazole-resistant strains C. alb 901 and C. alb 904, and had low toxicity against NIH/3T3 cells at the effective MIC range against fungi. Structure-activity relationship and docking studies of the derivatives suggest that the presence of the 2-fluoro-4-hydroxyphenyl and 1,2,3-triazole group enhance the antifungal activity of the compounds, which may be related to the interaction of the key groups with the amino acids surrounding the target enzyme.

Design, Synthesis and Biological Evaluation of Histone Deacetylase Inhibitors Based on Pyrrolo[2,3-d]pyrimidine and Pyrrolo[2,3-b]pyridine Scaffolds.

Histone deacetylases (HDACs) are validated targets for the development of anticancer drugs in epigenetics. We have designed and synthesized a series of novel HDAC inhibitors based on pyrrolo[2,3-d]pyrimidine and pyrrolo[2,3-b]pyridine scaffolds. Compound B3 {(E)-3-(4-(((1-(7H-pyrrolo[2,3-d]pyrimidin-4-yl)piperidin-4-yl)amino)methyl)phenyl)-N-hydroxyacrylamide} exhibits potent inhibitory activity against HDACs 1, 2, 3, 6, and 8 with IC50 values of 5.2, 6.0, 8.8, 4.4, and 173.0 nM, respectively. It exhibited potent antiproliferative effects against three tumour cell lines (IC50 values of 0.13, 0.37, and 1.11 μM, against MV-4-11, K562, and WSU-DLCL-2 cells, respectively) with two- to sixfold improvement relative to suberoylanilide hydroxamic acid (SAHA). Mechanistic studies on WSU-DLCL-2 cells revealed that B3 exhibits anticancer effects through the induction of G0 /G1 -phase arrest and promotion of apoptosis. The results of this study warrant further investigation of this compound series for the treatment of hematological malignancy.

Synthesis, 2D-NMR analysis, DFT, and optical nonlinear studies of a new cyclic imide

The synthesis of (11R,15S)-13-(3-hydroxyphenyl)-9,10-dihydro-9,10-[3,4]epipy-rroloanthracene-12,14‑dione, cyclic imide compound B3, via three path ways as a new compound is detailed. The new cyclic imide compound B3 is characterized by FTIR, Mass, 1 and 2D NMR (HSQC) and UV–vis. spectra. The cyclic imide compound B3 structure is studied using B3LYP method with the 6–311G* basis set level to carry out the density functional theory (DFT) calculations. The nonlinear optical)NLO(properties of the synthesized compound are studied using low power, continuous wave (cw), visible laser beam of wavelength 473 nm via two techniques viz., diffraction patterns (DPs) and Z-scan. Nonlinear refractive index (NLRI) of the compound B3 is calculated using both techniques where as high as 7.7 × 10−7 cm2/W at input power of 57 mW is obtained due to DPs technique. The all-optical switching (AOS) of the synthesized cyclic imide compound B3 is successfully examined using visible laser beams of wavelength 473 nm as controlling beam and 532 nm as the controlled beam based on the cross-passing technique.

Faecal metabolite deficit, gut inflammation and diet in Parkinson's disease: Integrative analysis indicates inflammatory response syndrome.

Gut-brain axis is widely implicated in the pathophysiology of Parkinson's disease (PD). We take an integrated approach to considering the gut as a target for disease-modifying intervention, using continuous measurements of disease facets irrespective of diagnostic divide. We characterised 77 participants with diagnosed-PD, 113 without, by dietary/exogenous substance intake, faecal metabolome, intestinal inflammation, serum cytokines/chemokines, clinical phenotype including colonic transit time. Complete-linkage hierarchical cluster analysis of metabolites discriminant for PD-status was performed. Longer colonic transitwas linked to deficits in faecal short-chain-fatty acids outside PD, to a 'tryptophan-containing metabolite cluster' overall. Phenotypic cluster analysisaggregated colonic transit with brady/hypokinesia, tremor, sleep disorder and dysosmia, each individually associated with tryptophan-cluster deficit. Overall, a faster pulse was associated with deficits in a metabolite cluster including benzoic acid and an imidazole-ring compound (anti-fungals) and vitamin B3 (anti-inflammatory) and with higher serum CCL20 (chemotactic for lymphocytes/dendritic cells towards mucosal epithelium). The faster pulse in PD was irrespective of postural hypotension. The benzoic acid-cluster deficit was linked to (well-recognised) lower caffeine and alcohol intakes, tryptophan-cluster deficit to higher maltose intake. Free-sugar intake was increased in PD, maltose intake being 63% higher (p = .001). Faecal calprotectin was 44% (95% CI 5%, 98%) greater in PD [p = .001, adjusted for proton-pump inhibitors (p = .001)], with 16% of PD-probands exceeding a cut-point for clinically significant inflammation compatible with inflammatory bowel disease. Higher maltose intake was associated with exceeding this calprotectin cut-point. Emerging picture is of (i) clinical phenotype being described by deficits in microbial metabolites essential to gut health; (ii) intestinal inflammation; (iii) a systemic inflammatory responsesyndrome.

Synthesis and Identification of Some Imino Chalcone Derivatives with Evaluating their Anti-oxidant Activity

This work involves the preparation of high yield iminochalcon compounds (B1-B15) through two parts. The first part involves the preparation of 2,4-dihydroxy Chalcone (A1-A15) by the condensation of 2,4-dihydroxy acetophenone with aryl aldehyde in the presence of sodium hydroxide (40%) as a catalyst. The second part includes the preparation of iminochalcon from the condensation of p-hydroxy aniline with 2,4-dihydroxy chalcone derivatives )A1-A15) in the presence of some drops of conc. H2SO4. Thin-layer chromatography ((TLC) was used to control the chemical reaction . These new derivatives were characterized by using FT-IR and 1H-NMR spectroscopy. These synthesized compounds were also assessed by the DPPH (2,2-diphenyl-1-picryl-hydrazyl-hydrate) free radical method, through which the compounds (B1-B15) were evaluated for their antioxidant activity. The compound B3 was found to have the strongest antioxidant activity (IC50= 23.91 μg/mL) as compared to that of the common standard of ascorbic acid (IC50=31.95 μg/mL).

Discovery of a PROTAC targeting ALK with invivo activity.

Anaplastic lymphoma kinase (ALK) was involved in the development of various cancer types. Although several ALK inhibitors have been advanced to clinical trials, the emergence of drug resistance has limited the clinical application of them. To overcome the drug resistance, proteolysis targeting chimeras (PROTACs) could be an alternative strategy. In this study, a series of ALK degraders were designed and synthesized. The degraders were developed through the conjugation of LDK378 and CRBN E3 ubiquitin ligase ligands. Among all the molecules, compound B3 showed potent selective inhibitory activity to ALK and can decrease the cellular levels of ALK fusion proteins in a concentration- and time-dependent manner in H3122cell line. Meanwhile, B3 showed improved anticancer activity invitro comparing with LDK378 and the antiproliferative activity to xenograft tumor model was acceptable. All the results demonstrated that ALK degrader B3 with invitro and invivo anti-cancer activities was valuable for further investigation.

1,3,4-Thiadiazolo (3,2-Α) Pyrimidine-6-Carbonitrile Scaffold as PARP1 Inhibitors.

1,3,4-thiadiazolo pyrimidine is a lead molecule that is versatile for a wide variety of biological activities and in continuation of our interest in establishing some novel heterocyclic compounds for antitumor activity. The objective of the study was to synthesize a series of 5-amino-7-(substituted aldehyde)-2[(naphthalene- 2-yloxy)methyl] -[1,3,4]thiadiazolo-[3,2-α]-pyrimidine-6- carbonitrile derivatives and evaluate their possible in vitro and in vivo anticancer activity. Herein, we report the synthetic scheme, which was followed for the preparation of a series of title compounds B1- B9 outlined in scheme 1. The intermediate 5-[(naphthalen-2- yloxy)methyl]-1,3,4-thiadiazolo- 2-amine was prepared by heating 2-naphthoxyacetic acid and thiosemicarbazide in the presence of phosphoryl chloride at a temperature of 65-75°C. The obtained compound reacted with malononitrile and an appropriate amount of aromatic and heteroaromatic aldehydes in refluxing ethanol yielded 5-amino-7-(substituted aldehyde)-2[(naphthalene-2-yloxy)methyl] -[1,3,4]thiadiazolo-[3,2-α]-pyrimidine-6- carbonitrile derivatives (B1 - B9). The purity of the synthesized compounds was ensured by various spectral analyses. In in silico molecular docking studies, compounds B3 and B9 show binding affinity like known PARP1 inhibitor olaparib. The cellular evaluation indicates that the anticancer profile of compounds B1, B3, and B9 is significant when compared to the standard drug (olaparib) against MDA-MB-232 cell line and compounds B3, B6, and B7 are the most active against MCF-7 cell lines. The most active compound B3 was subjected to acute oral toxicity studies by OECD 423 guidelines and in vivo anti-cancer studies were carried out using DMBA induced model. The in silico docking study of the newly synthesized compounds was performed; the results showed good binding mode in the active site of PARP1 enzyme. In silico ADME properties of synthesized compounds were also studied and showed good drug-like properties.

Design, synthesis and anti-TMV activity of novel α-aminophosphonate derivatives containing a chalcone moiety that induce resistance against plant disease and target the TMV coat protein

Plant viral diseases, known as “plant cancer”, with high contagiosity can substantially reduce crop quality and yield. To identify potential anti-tobacco mosaic virus (TMV) agents with different mechanisms, a series of novel α-aminophosphonate derivatives containing a chalcone moiety were designed and synthesized. Bioassay results revealed that some target compounds exhibited improved curative activity against TMV in vivo, and the EC50 value of compound B3 was 356.7 mg L−1. The activities of the defensive enzymes POD and CAT from tobacco leaves treated with B3 and B17 showed that these target compounds could improve the photosynthetic ability of the leaves and activate plant host resistance against TMV infection. The binding constant between B3 and TMV Coat Protein (CP) (2.51 × 108 M−1), calculated by the fluorescence titration experiment and docking results, revealed that B3 has a strong interaction with TMV CP. Further docking analysis revealed that B3 was embedded between two layers of the TMV CP, which was consistent with the 2:1 binding mode of TMV CP and B3 determined by the binding affinity experiment. The TEM morphological study of TMV treated with B3 and B17 indicated that this series of target compounds may trigger the disassembly of TMV by interacting directly with TMV CP. This study provides new insight for the discovery of antiviral compounds with two different mechanisms of action.

Dehydroberberine Analogue Nanoassemblies for Inducing and Self-Reporting Mitochondrial Dysfunction in Tumor Cells.

Mitochondria-targeting probes that allow us to induce and report mitochondrial dysfunction have become promising theranostic agents for cancer; however, the lack of selectivity toward tumor cells over normal tissue cells has impeded the treatment outcome. Herein, we develop 10 fluorescent dehydroberberine derivatives (B1-B10) capable of lighting up mitochondria and exerting moderate cytotoxicity against tumor cells. To enable the selectivity toward tumor cells over normal tissue cells, we introduced a lipophilic anion tetraphenylborate (TPB-) into the most potent compound B3+Cl- to drive molecular self-assembly into monodisperse organic nanoassemblies (B3NPs) in aqueous solution, which efficiently enhance the delivery of B3+ into HeLa cells assisted by an electrostatic interaction-driven anion-exchange process. Fluorescence imaging reveals that B3+ can initially accumulate in the mitochondria after entering HeLa cells, followed by inducing mitochondrial dysfunction and then migrating into the nucleus. Strong B3+ fluorescence translocating from mitochondria to nucleus can be monitored in real-time, allowing for self-reporting of mitochondrial dysfunction in HeLa cells. Moreover, we demonstrate that B3NPs exert significantly higher cytotoxicity against seven different tumor cells (e.g., U87MG, HeLa, MDA-MB-468, MDA-MB-435, MDA-MB-231, MCF-7, and HCT116 cells) compared to human normal tissue cells (e.g., HUVEC, HEK293). This work highlights the utility of the self-assembly approach to improve the cytotoxicity and selectivity of mitochondria-targeting agents against tumor cells.

Synthesis and biological evaluation of calycanthaceous alkaloid analogs

Starting from 9-methyl-1,2,3,4,9,9a-hexahydro-4aH-pyrido[2,3-b]indol-4a-ol, or indole-3-acetonitrile, 40 new calycanthaceous alkaloid analogs were synthesized in excellent yields. The prepared compounds were evaluated for biological activity against acetylcholinesterase and a broad range of plant pathogen fungi. The results of bioassays indicated that the majority of tested compounds displayed comparable or better in vitro bioactivity than the positive control. Notably, compounds b8 and b9 showed higher activity against Verticillium dahlia than chlorothalonil, with MIC values of 62.5 and 7.81 µg mL−1, respectively. Compound b3 had a higher activity against Bacillus cereus, with a MIC value of 15.63 µg mL−1. Compounds c2 and c11 revealed potent activity against acetylcholinesterase, with MIC values of 0.01 and 0.1 ng mL−1, respectively. Analysis of the molecular docking modes of c2 and c11 with Torpedo californica acetylcholinesterase indicated a medium strong hydrogen bond interaction between the hydroxyl groups of both the ligands and the phenolic hydroxyl of Try121 at a distance of approximately 2.4 Å. The results obtained in this study will be useful for the further design and structural optimization of calycanthaceous alkaloids as potential agrochemical lead compounds for plant disease control.

Synthesis and Anticancer Activity of 9-O-Pyrazole Alkyl Substituted Berberine Derivatives.

Berberine (BBR), an isoquinoline plant alkaloid isolated from plants such as Coptis chinensis and Hydrastis canadensis, own multiple pharmacological activities. In this study, seven BBR derivatives were synthesized and their anticancer activity against HeLa cervical and A549 human lung cancer cell lines were evaluated in vitro. The anti-cancer activity was measured by MTT assay, and apoptosis was demonstrated by the annexin V-FITC/PI staining assay. The intracellular oxidative stress was investigated through DCFH-DA assay. The molecular docking study was carried out in molecular operating environment (MOE). Compound B3 and B5 showed enhanced anti-cancer activity compared with BBR, the IC50 for compound B3 and B5 were significantly lower than BBR, and compound B3 at the concentration of 64 or 128 µM induced apoptosis in HeLa and A549 cell lines. The reactive oxygen species (ROS) was generated in both cell lines when treated with 100 µM of all the compounds, and compound B3 and B5 induced higher activity in the generation of ROS, while compound B3 exhibited the highest activity, these results are in accordance with the cytotoxicity results, indicating the cytotoxicity were mostly generated from the oxidative stress. In addition, molecular docking analysis showed that compound B3 had the greatest affinity with Hsp90. Upon binding, the protective function of Hsp90 was lost, which might explain its higher cytotoxicity from molecular interaction aspect. All the results demonstrated that compound B3 and B5 showed significantly higher anti-cancer ability than BBR, and compound B3 is a promising anticancer drug candidate.

Polypharmacological profile of 1,2-dihydro-2-oxo-pyridine-3-carboxamides in the endocannabinoid system

The endocannabinoid system (ECS) represents one of the major neuromodulatory systems involved in different physiological and pathological processes. Multi-target compounds exert their activities by acting via multiple mechanisms of action and represent a promising pharmacological modulation of the ECS. In this work we report 4-substituted and 4,5-disubstituted 1,2-dihydro-2-oxo-pyridine-3-carboxamide derivatives with a broad spectrum of affinity and functional activity towards both cannabinoid receptors and additional effects on the main components of the ECS. In particular compound B3 showed high affinity for CB1R (Ki = 23.1 nM, partial agonist) and CB2R (Ki = 6.9 nM, inverse agonist) and also significant inhibitory activity (IC50 = 70 nM) on FAAH with moderate inhibition of ABHD12 (IC50 = 2.5 μΜ). Compounds B4, B5 and B6 that act as full agonists at CB1R and as partial agonists (B5 and B6) or antagonist (B4) at CB2R, exhibited an additional multi-target property by inhibiting anandamide uptake with sub-micromolar IC50 values (0.28–0.62 μΜ). The best derivatives showed cytotoxic activity on U937 lymphoblastoid cells. Finally, molecular docking analysis carried out on the three-dimensional structures of CB1R and CB2R and of FAAH allowed to rationalize the structure-activity relationships of this series of compounds.

Three new water-soluble fluorescent organic nanoparticles with embedded structure: Structure-activity relationship and two-photon bio-imaging application

Three benzothiazole-based two-photon absorption (2PA) chromophores (B1-3) were synthesized and the optical properties were investigated. The results illustrated the largest fluorescence quantum yield and effective 2PA cross-sections reached to 0.81 for compound B1 and 1013 GM for compound B3 in tetrahydrofuran solutions, respectively. Furthermore, the water-soluble fluorescent organic nanoparticles (FONs) possessing an embedded structure were prepared from the three compounds and Pluronic F127, which were successfully applied on two-photon nuclear envelope imaging.

Pharmacological evaluation of 9,10-dihydrochromeno[8,7-e][1,3]oxazin-2(8H)-one derivatives as potent anti-inflammatory agent.

Non-steroidal anti-inflammatory drugs (NSAIDs) are the most widely administered drugs for the treatment of inflammation. However, they usually cause some unexpected side effects. Coumarins and their derivatives exhibit broad-spectrum biological activities. In order to develop new anti-inflammatory drugs with high anti-inflammatory activity and less side effects, a series of 9-substituted-9,10-dihydrochromeno[8,7-e][1,3]oxazin-2(8H)-one derivatives were designed, synthesized, and screened for their anti-inflammatory activities. We investigated the effect of compound 9-(2-chlorophenyl)-9,10-dihydrochromeno[8,7-e][1,3]oxazin-2(8H)-one (B3) on lipopolysaccharide (LPS)-induced cytokine levels in RAW 264.7 cells at concentrations between 6.25μg/ml and 25μg/ml. Concentrations of tumor necrosis factor-α (TNF-α) and interleukin-6 (IL-6) were measured by enzyme-linked immunosorbent assay (ELISA). Moreover, mitogen-activated protein kinase (MAPK) and nuclear factor-κB (NF-κB) activation was investigated by western blot assay. Compound B3 could inhibit inflammatory responses via suppression of the NF-κB and MAPK signaling pathways. Docking study of the prepared compounds was performed for the study of interaction of molecules with the active site of TNF-α. 9,10-Dihydrochromeno[8,7-e][1,3]oxazin-2(8H)-one derivatives showed anti-inflammatory activity. Compound B3 was the most potent. The results of this study are encouraging further investigations to develop compound B3 as a novel therapeutic agent for inflammatory disorders.

KDM4/JMJD2 Histone Demethylase Inhibitors Block Prostate Tumor Growth by Suppressing the Expression of AR and BMYB-Regulated Genes

Histone lysine demethylase KDM4/JMJD2s are overexpressed in many human tumors including prostate cancer (PCa). KDM4s are co-activators of androgen receptor (AR) and are thus potential therapeutic targets. Yet to date few KDM4 inhibitors that have anti-prostate tumor activity in vivo have been developed. Here, we report the anti-tumor growth effect and molecular mechanisms of three novel KDM4 inhibitors (A1, I9, and B3). These inhibitors repressed the transcription of both AR and BMYB-regulated genes. Compound B3 is highly selective for a variety of cancer cell lines including PC3 cells that lack AR. B3 inhibited the in vivo growth of tumors derived from PC3 cells and ex vivo human PCa explants. We identified a novel mechanism by which KDM4B activates the transcription of Polo-like kinase 1 (PLK1). B3 blocked the binding of KDM4B to the PLK1 promoter. Our studies suggest a potential mechanism-based therapeutic strategy for PCa and tumors with elevated KDM4B/PLK1 expression.

Synthesis, analgesic and anti-inflammatory activities of novel mannich bases of benzimidazoles

A series of novel mannich bases of 2-substituted benzimidazoles was synthesized by the reaction of 2-substituted benzimidazoles with corresponding aldehyde and acetophenones. The structures of all synthesized compounds were confirmed by elemental analysis, IR, 1H-NMR, 13C-NMR and LCMS. The compounds were evaluated for in vivo analgesic and in vivo anti-inflammatory activities by a tail flick method and carrageenan-induced rat paw edema test respectively. Among all the compounds synthesized, compound A1 and B3 exhibited significant analgesic and anti-inflammatory activities. Acute ulcerogenicity studies showed that compound A1 and B3 were devoid of gastrointestinal toxicities.

ANTIMICROBIAL ACTIVITY OF FLAVONOID COMPOUND ISOLATED FROM INULA GREAVEOLENS L. PLANT ON SELECTED PATHOGENIC BACTERIA

The antibacterial activity of the flavonoid compound (B3) isolated from Inula greaveolens plant by column – chromatography was determined against several of clinical microbial isolates including Gram positive: ( Streptococcus spp. Staphylococcus aureus ) and isolates of Gram negative : ( Klebsiella pneumonia, Pseudomonas aeroginosa and Esherichia coli ) by using three concentrations of the extract (125 mg /ml , 250mg /ml ,500 mg /ml ).The results revealed that the falvonoid compound B3 has varying degrees of inhibition tested microorganisms. The cytotoxic activity of the falvonoid compound (B3) was determined against the fresh human red blood celles with several concentrations of the extract and the results shown that flavonoid compound did not had toxicity against the human red blood cells.

Synthesis and Evaluation of 2, 4, 5 - Trisubstituted and 1, 2, 4, 5 Tetrasubstituted Imidazole as Antimicrobial Agents

A series of 2,4,5-trisubstituted (A1-A15) and 1,2,4,5-tetrasubstituted (B1-B7) imidazole derivatives were synthesized by the reaction of Benzil, aldehyde, ammonium acetate, aromatic primary amines using catalyst tetrabutylammoniumbromide in isopropanol. Structures of these compounds were elucidated by spectral (IR, 1 H NMR) analysis. The newly synthesized compounds were screened for antifungal and antibacterial activities. The activity was measured in terms of zone of inhibition and compared with standard drug. Compounds A4,A7,A8,A10,A12,A14,A15,B1,B3,B5 and B6 have shown good antibacterial activity against std. Norfloxacin and Compound A2,A3,A6,A7,A9,A10,A14,A15,B2,B3,B4,B6 and B7 exhibited good antifungal activities against std. Clotrimazole, and other compound shows moderate activity.

Substituted tetrahydroisoquinoline compound B3 inhibited P-glycoprotein-mediated multidrug resistance in-vitro and in-vivo

P-glycoprotein (P-gp) mediated multidrug resistance (MDR) is one of the main obstacles in tumour chemotherapy. A promising approach to reverse MDR is the combined use of nontoxic and potent P-gp inhibitor with conventional anticancer drugs. We have examined the potential of a newly synthesized tetrahydroisoquinoline derivative B3 as a MDR-reversing agent. The MTT (3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide) assay was used to examine the effect of B3 on the cytotoxicity in K562/A02 and MCF-7/ADM cells caused by doxorubicin (adriamycin). Accumulation and efflux of P-gp substrate rhodamine123 in K562/A02 and primary cultured rat brain microvessel endothelial cells (RBMECs) were measured to evaluate the inhibitory effect of B3 on P-gp. The K562/A02 xenograft model in nude mice was established to examine MDR-reversing efficacy of B3 in-vivo. The results indicated that co-administration of B3 resulted in an increase on chemosensitivity of K562/A02 and MCF-7/ADM cells to doxorubicin in a dose-dependent manner. Rhodamine123 accumulation in K562/A02 cells and RBMECs were significantly enhanced after the incubation with various concentrations of B3. Furthermore, B3 inhibited the efflux of rhodamine123 from RBMECs. Co-administration of B3 with doxorubicin significantly decreased weight and volume of tumour in nude mice. In conclusion, B3 is a novel and potent MDR reversal agent with the potential to be an adjunctive agent for tumour chemotherapy.