Understanding the role of Pax5 in development of taxane-resistant neuroendocrine like prostate cancers.

Resistance to the current Androgen Receptor Signaling Inhibitor (ARSI) therapies has led to higher incidences of therapy-induced neuroendocrine-like prostate cancer (t-NEPC). This highly aggressive subtype with predominant small cell-like characteristics is resistant to taxane chemotherapies and has a dismal overall survival. t-NEPCs are mostly treated with platinum-based drugs with a combination of etoposide or taxane and have less selectivity and high systemic toxicity, which often limit their clinical potential. During t-NEPC transformation, adenocarcinomas lose their luminal features and adopt neuro-basal characteristics. Whether the adaptive neuronal characteristics of t-NEPC are responsible for such taxane resistance remains unknown. Pathway analysis from patient gene-expression databases indicates that t-NEPC upregulates various neuronal pathways associated with enhanced cellular networks. To identify transcription factor(s) (TF) that could be important for promoting the gene expression for neuronal characters in t-NEPC, we performed ATAC-Seq, acetylated-histone ChIP-seq, and RNA-seq in our NE-like cell line models and analyzed the promoters of transcriptionally active and significantly enriched neuroendocrine-like (NE-like) cancer-specific genes. Our results indicate that Pax5 could be an important transcription factor for neuronal gene expression and specific to t-NEPC. Pathway analysis revealed that Pax5 expression is involved in axonal guidance, neurotransmitter regulation, and neuronal adhesion, which are critical for strong cellular communications. Further results suggest that depletion of Pax5 disrupts cellular interaction in NE-like cells and reduces surface growth factor receptor activation, thereby, sensitizing them to taxane therapies. Moreover, t-NEPC specific hydroxymethylation of Pax5 promoter CpG islands favors Pbx1 binding to induce Pax5 expression. Based on our study, we concluded that continuous exposure to ARSI therapies leads to epigenetic modifications and Pax5 activation in t-NEPC, which promotes the expression of genes necessary to adopt taxane-resistant NE-like cancer. Thus, targeting the Pax5 axis can be beneficial for reverting their taxane sensitivity.

Glabridin synergy with norfloxacin induces ROS in multidrug resistant Staphylococcus aureus.

Glabridin (Glb), a polyphenolic flavonoid inhibits the growth of MDRSA (Multidrug resistant S. aureus) 4627 by inducing ROS. Glb in combination with Norfloxacin (Nor) synergistically induced oxidative stress. Increased ROS/RNS levels, in particular, affected macromolecules' (DNA, lipid, protein) integrity and distorted cell morphology. We found correlation between drug-effects and up-/down-regulation of oxidative stress-related as well as MDR genes. These findings could considerably potentiate the dosing routine of Nor in combination with Glb, which holds a promising prospective as a antibacterial agent against S. aureus.

Insights from a Pan India Sero-Epidemiological survey (Phenome-India Cohort) for SARS-CoV2.

To understand the spread of SARS-CoV2, in August and September 2020, the Council of Scientific and Industrial Research (India) conducted a serosurvey across its constituent laboratories and centers across India. Of 10,427 volunteers, 1058 (10.14%) tested positive for SARS-CoV2 anti-nucleocapsid (anti-NC) antibodies, 95% of which had surrogate neutralization activity. Three-fourth of these recalled no symptoms. Repeat serology tests at 3 (n = 607) and 6 (n = 175) months showed stable anti-NC antibodies but declining neutralization activity. Local seropositivity was higher in densely populated cities and was inversely correlated with a 30-day change in regional test positivity rates (TPRs). Regional seropositivity above 10% was associated with declining TPR. Personal factors associated with higher odds of seropositivity were high-exposure work (odds ratio, 95% confidence interval, p value: 2.23, 1.92-2.59, <0.0001), use of public transport (1.79, 1.43-2.24, <0.0001), not smoking (1.52, 1.16-1.99, 0.0257), non-vegetarian diet (1.67, 1.41-1.99, <0.0001), and B blood group (1.36, 1.15-1.61, 0.001).

Silymarin, a polyphenolic flavonoid impede Plasmodium falciparum growth through interaction with heme.

A polyphenolic flavonoid, Silymarin isolated from Silybum marianum is widely known for its hepatoprotective action. In the present study anti-plasmodial activity of Silymarin has been demonstrated for the first time having IC50 of 14 ± 0.33 µM against the NF-54 strain of P. falciparum with high selectivity index (>100). The parasitostatic action is exerted through inhibition of ß-hematin/hemozoin formation which is due to the interaction (Kd = 3.63 ± 0.9µM) of silymarin with free heme in a Stoichiometry of 1:1 Silymarin: heme complex resulting into heme-induced membrane damage in the parasite. Silymarin could hinder the glutathione and hydrogen peroxide-induced heme detoxification. Silymarin also induces apoptosis in the parasite through the elevation of caspase-3 level in a dose-dependent manner. Results from the docking studies suggest that Silymarin interacts with heme.

Synthesis of thymol-based pyrazolines: An effort to perceive novel potent-antimalarials.

A series of thymol based substituted pyrazolines and chalcones was synthesized and evaluated for antimalarial activity, using in-vitro and in-vivo malaria models. All the target compounds (5a-k and 6a-j) were found to be active against human malaria parasite strain Plasmodium falciparum NF54. Among all, compounds 5e and 5f of chalcone series and 6c and 6f of pyrazoline series exhibited prominent antimalarial activity with IC50 less than 3 and 2 µM respectively, while other pyrazolines also significantly inhibited the P. falciparum with IC50 less than 10 µM. The designed pharmacophores were found to be effective against P. falciparum. Compound 6f was found to be able to retard malaria progression in mice. This was evident through decreased parasitemia, increased mean survival time and hemoglobin content in the treated animals. Moreover, 6f was observed as an inhibitor of heme polymerization pathway of the malaria parasite. It also inhibited free heme degradation, which could be possibly responsible for higher reactive oxygen species (ROS) in parasite, thus inhibiting the rapid proliferation of the parasite. In addition to this, compound 6f was found to be non-toxic with a good selectivity index. Based on these observations, the compound 6f could be taken up for further antimalarial lead optimization studies.

The essential oil from Citrus limetta Risso peels alleviates skin inflammation: In-vitro and in-vivo study.

ETHNOPHARMACOLOGICAL RELEVANCE: Citrus fruit peels are traditionally used in folk medicine for the treatment of skin disorders but it lacks proper pharmacological intervention. Citrus limetta Risso (Rutaceae) is an important commercial fruit crops used by juice processing industries in all continents. Ethnopharmacological validation of an essential oil isolated from its peels may play a key role in converting the fruit waste materials into therapeutic value added products. AIM OF THE STUDY: To evaluate the chemical and pharmacological (in-vitro and in-vivo) profile of essential oil isolated from Citrus limetta peels (Clp-EO) against skin inflammation for its ethnopharmacological validation. MATERIALS AND METHODS: Hydro-distilled essential oil extracted from Citrus limetta peels (Clp-EO) was subjected to gas chromatography (GC) analysis for identification of essential oil constituents and its anti-inflammatory evaluation through in vitro and in vivo models. RESULTS: Chemical fingerprint of Clp-EO revealed the presence of monoterpene hydrocarbon and limonene is the major component. Pre-treatment of Clp-EO to the macrophages was able to inhibit the production of pro-inflammatory cytokines (TNF-α, IL-6, IL-1ß) in LPS-induced inflammation as well as the production of reactive oxygen species (ROS) in H2O2-induced oxidative stress. In in-vivo study, topical application of Clp-EO was also able to reduce the 12-O-tetradecanoylphorbol-13-acetate (TPA)-induced ear thickness, ear weight, lipid peroxidation, pro-inflammatory cytokines production and ameliorate the histological damage in the ear tissue. In-vitro and in-vivo toxicity study indicate that it is safe for topical application on skin. CONCLUSION: These findings suggested the preventive potential of Clp-EO for the treatment of inflammation linked skin diseases.

A rare case of recurrence of primary spinal neurocysticercosis mimicking an arachnoid cyst.

Neurocysticercosis (NCC) is a common parasitic infection of the central nervous system but isolated primary spinal NCC is of very rare occurrence. The authors report a case of 44-year-old male, a postoperative case of multiple spinal NCC lesion excision 2 years ago, who presented with cauda equina syndrome and magnetic resonance imaging revealed a lesion mimicking an arachnoid cyst in the D1-9 region of the spinal cord. On intraoperative surgical exposure multiple cysts were found and excised. The suspicion of recurrence of NCC was confirmed by histopathology. Postoperatively there was significant improvement in neurological symptoms of the patient. Recurrence of primary spinal NCC should be considered in differential diagnosis of an arachnoid cyst if there is a definitive past history.

Adjuvant effect of Asparagus racemosus Willd. derived saponins in antibody production, allergic response and pro-inflammatory cytokine modulation.

The study manifests the immunoadjuvant potential of saponin rich fraction from Asparagus racemosus in terms of cellular and humoral immune response that can be exploited against microbial infections. Asparagus racemosus (AR) has been attributed as an adaptogen and rasayana in traditional medication systems for enhancing the host defence mechanism. Spectrophotometric and HPTLC analysis ensured the presence of saponins. The saponin rich fractions were tested for immunoadjuvant property in ovalbumin immunised mice for the humoral response, quantified in terms of prolonged antibody production upto a duration of 56days. Proinflammatory cytokines (IL-6 and TNF) were estimated for the cellular immune response in LPS stimulated primary murine macrophages. The safety evaluation in terms of cytotoxicity and allergic response has also been evaluated through in-vitro (MTT) and in-vivo (IgE) respectively. ARS significantly inhibited the pro-inflammatory cytokines, in LPS stimulated murine macrophages with no intrinsic cytotoxicity. The significant increase in IgG production infers the utility of ARS for prolonged humoral response. Further, the antigen specific response of IL-12 at early stage and IgE titres also suggests the generation of cellular immune response and low allergic reaction respectively, as compared to conventional adjuvants. IL-6 and TNF fluctuations in LPS stimulated and non-stimulated macrophages along with IgG and IL-12 also confirmed the Th1/Th2 modulating effect of ARS. The study indicates potential effect of ARS as an adjuvant for the stimulation of cellular immune response in addition to generating a sustained adaptive response without any adverse effects paving way for further validation with pathogenic organisms.

Gallic acid-based indanone derivative interacts synergistically with tetracycline by inhibiting efflux pump in multidrug resistant E. coli.

The purpose of the present study was to study the synergy potential of gallic acid-based derivatives in combination with conventional antibiotics using multidrug resistant cultures of Escherichia coli. Gallic acid-based derivatives significantly reduced the MIC of tetracycline against multidrug resistant clinical isolate of E. coli. The best representative, 3-(3',4,'5'-trimethoxyphenyl)-4,5,6-trimethoxyindanone-1, an indanone derivative of gallic acid, was observed to inhibit ethidium bromide efflux and ATPase which was also supported by in silico docking. This derivative extended the post-antibiotic effect and decreased the mutation prevention concentration of tetracycline. This derivative in combination with TET was able to reduce the concentration of TNFα up to 18-fold in Swiss albino mice. This derivative was nontoxic and well tolerated up to 300 mg/kg dose in subacute oral toxicity study in mice. This is the first report of gallic acid-based indanone derivative as drug resistance reversal agent acting through ATP-dependent efflux pump inhibition.

A polyphenolic flavonoid glabridin: Oxidative stress response in multidrug-resistant Staphylococcus aureus.

Glabridin a polyphenolic flavonoid from Glycyrrhiza glabra is known to possess several therapeutic properties. In the present study, we report for the first time the in vitro antibacterial activity (MIC values ranging from 3.12 to 25 µg/mL) of glabridin against multidrug-resistant clinical isolates of S. aureus by inducing oxidative stress. Increased levels of H2O2 and NO were observed in a dose-dependent manner after treatment of glabridin that further affected macromolecules such as DNA, lipids, and proteins. Surprisingly, glabridin was found to possess antioxidant properties when used at lower concentrations using three different methods including DPPH, FRAP, and SOD assays. These observations were further validated through the expression analysis of oxidative stress-responsive genes using qRT-PCR wherein glabridin was observed to up- and down-regulate these genes at lower and higher concentrations, respectively. In in vitro combination experiments, glabridin was found to reduce the MIC of different antibiotics such as norfloxacin, oxacillin, and vancomycin by up to 4-fold, while the MIC of glabridin itself was found to be reduced by up to 8-fold in the presence of antibiotics. A synergistic interaction was observed between norfloxacin and glabridin when used in combination against multidrug-resistant clinical isolate SA 4627 of Staphylococcus aureus at much lower concentrations, indicating the suitability of glabridin in combination therapy.

A novel approach for development and characterization of effective mosquito repellent cream formulation containing citronella oil.

Citronella essential oil (CEO) has been reported as an excellent mosquito repellent; however, mild irritancy and rapid volatility limit its topical application. It was aimed to develop a nonirritant, stable, and consistent cream of CEO with improved residence time on skin using an industrial approach. Phase inversion temperature technique was employed to prepare the cream. It was optimized and characterized based on sensorial evaluation, emulsification, and consistency in terms of softness, greasiness, stickiness, and pH. The optimum batch (B5) was evaluated for viscosity (90249.67±139.95 cP), texture profile with respect to firmness (38.67±0.88 g), spreadability (70.33±0.88 mJ), and extrudability (639.67±8.09±0.1 mJ) using texture analyzer along with two most popular marketed products selected as reference standard. Subsequently, B5 was found to be stable for more than 90 days and showed enhanced duration of mosquito repellency as compared to CEO. HS-GC ensured the intactness of CEO in B5. Investigated primary irritation index (PII 0.45) positioned B5 into the category of irritation barely perceptible. The pronounced texture profile and stability of B5 with extended residence time and less PII revealed its potential application in industry and offered a promising alternative to the marketed products of synthetic origin.

Synthesis of neolignans as microtubule stabilisers.

Tubulin is a well established target for anticancer drug development. Lignans and neolignans were synthesized as tubulin interacting agents. Neolignans 10 and 19 exhibited significant anticancer activity against MCF-7 and MDAMB-231 human breast cancer cell lines. Both the compounds effectively induced stabilization of microtubule at 4 and 20 µM concentrations respectively. Neolignan 10 induced G2/M phase arrest in MCF-7 cells. Docking experiments raveled that 10 and 19 occupied the same binding pocket of paclitaxel with some difference in active site amino acids and good bioavailability of both the compounds. In in vivo acute oral toxicity 10 was well tolerated up to 300 mg/kg dose in Swiss-albino mice.

Diclofenac is more effective for post-operative analgesia in patients undergoing lower abdominal gynecological surgeries: A comparative study.

AIM: The present study aimed to compare the efficacy of injectable diclofenac intramuscularly (IM), injection paracetamol intravenously (IV), or a combination of both to provide post-operative analgesia in patients undergoing lower abdominal gynecological surgeries. MATERIALS AND METHODS: A total of 90 female patients (American Society of Anesthesiologists I and II), aged 20-50 years, scheduled for elective total abdominal hysterectomy with or without bilateral salpingo-oophorectomy were randomized to receive 75 mg diclofenac IM 8 hourly (Group D) or 1 g paracetamol IV 8 hourly (Group P) or a combination of both 8 hourly (Group PD) for 24 h post-operative period from the start of surgery. The primary outcome measured was the requirement of rescue analgesic (tramadol), the secondary outcomes measured included visual analog score (VAS) for pain, time until first rescue analgesic administration, patient satisfaction score and any side effects. RESULTS: The requirement of rescue analgesic was significantly lower in Groups D and PD compared to Group P. Mean (standard deviation) tramadol requirement during 24 h was 56.67 (62.60) mg, 20.00 (40.68) mg and 20.00 (40.68) mg in the Groups P, D and PD respectively. Less number of patients in Groups D and PD (20% in both the groups) required rescue analgesic compared to Group P (50%). The VAS showed a significant decrease in Groups D and PD compared to Group P between 4 and 12 h post-operatively. However, Group PD showed no significant difference when compared to Group D alone. CONCLUSION: Injection diclofenac IM is more effective than paracetamol IV in terms of rescue analgesic requirement, but the combination of diclofenac IM and paracetamol IV provides no added advantage over diclofenac IM alone.

Glabridin induces oxidative stress mediated apoptosis like cell death of malaria parasite Plasmodium falciparum.

Plants are known as the source of novel agents for developing new antimalarial drugs. Glabridin is a polyphenolic flavonoid, a main constituent in the roots of Glycyrrhiza glabra possesses various biological activities. However, its anti-plasmodial activity is unexplored. In the present work, it is for the first time demonstrated that glabridin inhibits Plasmodium falciparum growth in vitro with an IC50 23.9±0.43µM. Glabridin showed poor cytotoxicity in vitro with an IC50 246.6±0.88µM against Vero cell line and good selectivity index (9.6). In erythrocytic cycle, trophozoite stage was found to be most sensitive to glabridin. In silico study showed that glabridin inhibits Pf LDH enzyme activity by acting on NADH binding site. Glabridin induced oxidative stress by the generation of reactive oxygen and nitrogen species. Glabridin could induce apoptosis in parasite as evidenced by the depolarization of mitochondrial membrane potential (Δψm), activation of caspase like proteases and DNA fragmentation. These results indicate that glabridin exhibits antiplasmodial activity and is suitable for developing antimalarial agent from a cheap and sustainable source.

Effect of a single preoperative dose of sublingual misoprostol on intraoperative blood loss during total abdominal hysterectomy.

OBJECTIVE: To investigate whether use of preoperative misoprostol can reduce blood loss during total abdominal hysterectomy (TAH). METHODS: In a randomized double-blind placebo-controlled trial at a tertiary care hospital in Kolkata, India, between March 2011 and April 2012, women (n=132) undergoing TAH with or without bilateral salpingo-oophorectomy for symptomatic myomas were randomly allocated to receive either 400 µg of misoprostol or placebo 30 minutes before surgery. The primary outcome measure was intraoperative blood loss was. The secondary outcomes were postoperative drop in hemoglobin, need for blood transfusion, and incidence of adverse effects. RESULTS: The 2 groups were similar with regard to demographic and clinical characteristics. There was a significant reduction of blood loss during TAH after sublingual administration of misoprostol compared with placebo before surgery (356 mL vs 435 mL; P=0.049). The mean postoperative hemoglobin concentration was higher (10.5 g/dL vs 9.5 g/dL; P<0.001) and the postoperative drop in hemoglobin was smaller (1.1g/dL vs 1.9 g/dL; P=0.004) in the misoprostol group than in the placebo group. No significant adverse effects occurred in either group. CONCLUSION: The results showed that a single dose of misoprostol administered before abdominal hysterectomy resulted in a significant reduction of blood loss with minimal adverse effects. Clinical Trial Registry India (www.ctri.nic.in): CTRI/2011/091/000216.

Nyctanthes arbor-tristis positively affects immunopathology of malaria-infected mice prolonging its survival.

In order to search for new products that display antimalarial and immunomodulatory mechanisms that complement direct antiparasitic activity, a set of in vitro and in vivo experiments were designed to evaluate the effect of Nyctanthes arbor-tristis in Plasmodium berghei infected mice. Three extracts of N. arbor-tristis leaves from varying concentrations of alcohol and water were considered for their potential to suppress expression of pro-inflammatory mediators from macrophages primed with lipopolysaccharide. The ethanolic extract, which lowered the pro-inflammatory mediators [tumour necrosis factor (TNF), 13.52-55.83 %; interleukin-6 (IL-6), 0-17.29 %; and NO, 39.37-81.63 %], was selected to be examined in malaria (P. berghei) infected mice. Corroborating the in vitro results, it was observed that the extract could normalise the TNF (78 %) and IL-6 (70.35 %) optimally at 1 g/kg, thus retarding the pathological process in infected mice and increasing the mean survival time from 10.6 to 15.6 days. There were no signs of toxicity in the acute oral toxicity test up to 2 g/kg. (1)H NMR of the biologically active extract was obtained to ensure the presence of the compound of interest, i.e., iridoid glycoside. The quality and the reproducibility of results were ensured by means of achieving characteristic high-performance liquid chromatography fingerprint of the extract.

Nyctanthes arbor-tristis Linn--a critical ethnopharmacological review.

ETHNOPHARMACOLOGICAL RELEVANCE: Nyctanthes arbor-tristis (Oleaceae) is a mythological plant; has high medicinal values in Ayurveda. The popular medicinal use of this plant are anti-helminthic and anti-pyretic besides its use as a laxative, in rheumatism, skin ailments and as a sedative. Vitally, the natives plant it in their home gardens to pass on its medicinal usage to oncoming generations. AIM OF THE REVIEW: The present review encompasses an ethnopharmacological evaluation focusing on information on the chemical constituents, pharmacological actions and toxicology in order to reveal the therapeutic potential and gaps requiring research involvement. MATERIALS AND METHODS: The present review is based on searches in Scifinder(®), Pubmed (National Library of Medicine) and books published on the subject during the period 1933 to 2012. RESULTS: Nyctanthes arbor-tristis is most important in local and traditional medicines especially in India for treating intermittent fevers, arthritis and obstinate sciatica. Crude extracts and isolated compounds from the plant were shown to be pharmacologically active against inflammation, malaria, viral infection, leishmanisis and as an immunostimulant. The major class of biologically active compounds are the iridoid glucosides incl., Arbortristoside A, B and C from the seeds active as anticancer, anti-leishmania, anti-inflammatory, anti-allergic, immunomodulatory and antiviral. Other molecules; calceolarioside A, 4-hydroxyhexahydrobenzofuran-7one and ß-sitosterol from leaves have been reported to be active as anti-leishmanial, anticancer and anti-inflammatory, respectively. The crude extracts have been found to be safe with an LD50 of 16gm/kg, while the LD50 of arbortristoside-A isolated from the seeds was found to be 0.5g/kg. CONCLUSION: Mostly in-vitro or in some cases in-vivo models provide some evidence especially in the treatment of inflammatory conditions like arthritis, fevers related to malaria and protozoan diseases especially leishmaniasis. The only clinical study found, is for treating malaria, but with crude extract only. Further, more detailed safety data pertaining to the acute and sub-acute toxicity, cardio and immunotoxicity also needs to be generated for crude extracts or pure compounds.

Novel anti-inflammatory phytoconstituents from Desmodium gangeticum.

A new aliphatic enone, (17Z,20Z)-hexacosa-17,20-dien-9-one (3), and one new bisindole alkaloid, gangenoid (6), together with seven known compounds were isolated from the roots and aerial parts of Desmodium gangeticum (family: Leguminosae). All the compounds except 2 and 7 were isolated from this plant for the first time, which may be of chemotaxonomic importance. Structures of compounds 3 and 6 were determined on the basis of their detailed spectroscopic analyses (NMR, IR and mass). In addition, compounds 3 and 6 were investigated for their effects on lipopolysaccharide-stimulated macrophages for the production of pro-inflammatory cytokines such as tumour necrosis factor-α and interleukin-6.

Anticancer activity, toxicity and pharmacokinetic profile of an indanone derivative.

The present study describes anticancer effect of gallic acid based indanone derivative (1). Indanone 1 exhibited in vivo anticancer activity against Erhlich ascites carcinoma in Swiss albino mice by inhibiting tumor growth by 54.3% at 50 mg/kg b.wt. It showed antitubulin effect by inhibiting tubulin polymerase enzyme. In cell cycle analysis, it inhibited G2/M phase and induced apoptosis. It significantly suppressed VEGF-R1, VEGF-R2 and HIF-α in human breast cancer MCF-7 cells, thus exhibiting antiangiogenic activity. In acute oral toxicity, indanone 1 was well tolerated and was found to be non-toxic up to 1000 mg/kg b.wt. in Swiss albino mice. Pharmacokinetic studies in rabbits revealed rate of absorption, half life, volume of distribution with high plasma and blood clearance after i.v. administration. Indanone 1, is a safe and moderately active anticancer agent.

Anti-Helicobacter pylori potential of artemisinin and its derivatives.

The antimalarial drug artemisinin from Artemisia annua demonstrated remarkably strong activity against Helicobacter pylori, the pathogen responsible for peptic ulcer diseases. In an effort to develop a novel antimicrobial chemotherapeutic agent containing such a sesquiterpene lactone endoperoxide, a series of analogues (2 natural and 15 semisynthetic molecules), including eight newly synthesized compounds, were investigated against clinical and standard strains of H. pylori. The antimicrobial spectrum against 10 H. pylori strains and a few other bacterial and fungal strains indicated specificity against the ulcer causing organism. Of five promising molecules, a newly synthesized ether derivative ß-artecyclopropylmether was found to be the most potent compound, which exhibited MIC range, MIC(90), and minimum bactericidal concentration range values of 0.25 to 1.0 µg/ml, 1.0 µg/ml, and 1 to 16 µg/ml, respectively, against both resistant and sensitive strains of H. pylori. The molecule demonstrated strong bactericidal kinetics with extensive morphological degeneration, retained functional efficacy at stomach acidic pH unlike clarithromycin, did not elicit drug resistance unlike metronidazole, and imparted sensitivity to resistant strains. It is not cytotoxic and exhibits in vivo potentiality to reduce the H. pylori burden in a chronic infection model. Thus, ß-artecyclopropylmether could be a lead candidate for anti-H. pylori therapeutics. Since the recurrence of gastroduodenal ulcers is believed to be mainly due to antibiotic resistance of the commensal organism H. pylori, development of a candidate drug from this finding is warranted.