Mahendar Porika

Indolylmethylene benzo[h]thiazolo[2,3-b]quinazolinones: Synthesis, characterization and evaluation of anticancer and antimicrobial activities

A series of novel 10-((1H-indol-3-yl)methylene)-7-aryl-7,10-dihydro-5H-benzo[h]thiazolo[2,3-b]quinazolin-9(6H)-ones (8a-t) have been synthesized in good yields by the reaction of benzo[h]quinazoline-2(1H)-thiones (4a-f) with 2-chloro-N-phenylacetamide (5) followed by Knoevenagel condensation with various indole-3-carbaldehydes (7a-d) under conventional method. All the synthesized compounds were characterized by spectral studies and screened for their in vitro anticancer and antimicrobial activities. Compound 8c has exhibited excellent activity against MCF-7 (breast cancer cell line) than the standard drug Doxorubicin. Compound 8d against both the cancer cell lines, 8q against MCF-7 and 8c, 8h against HepG2 have also shown good activity. Remaining compounds have shown moderate activity against both the cell lines. Antimicrobial activity revealed that, the compound 8q and 8t against Staphylococcus aureus and 8i, 8k, 8l, 8q &8t against Klebsiella pneumoniae have shown equipotent activity on comparing with the standard drug Streptomycin. Remaining compounds have shown significant antibacterial and comparable antifungal activities against all the tested microorganisms.

Pterostilbene as a potential novel telomerase inhibitor: molecular docking studies and its in vitro evaluation.

Pterostilbene is a naturally occurring dimethyl ether analog of resveratrol identified in several plant species. Telomerase is important in tumor initiation and cellular immortalization. Given the striking correlations between telomerase activity and proliferation capacity in tumor cells, telomerase had been considered as a potentially important molecular target in cancer therapeutics. Molecular docking studies were performed on pterostilbene with the crystal structure of telomerase (3DU6). Pterostilbene was evaluated for its in vitro cytotoxicity in breast (MCF7) and lung cancer (NCI H-460) cell lines, antimitotic activity in green grams and telomerase activity. Curcumin was used as a standard. Docking results indicated good interaction between pterostilbene and the active site of telomerase and the docked energy of pterostilbene was -7.10 kcal/mol. Pterostilbene showed strong inhibitory effect on in vitro telomerase activity and cell growth in both the cell lines tested in a dose dependent manner. Cancer cells treated with 80 µM pterostilbene exhibited significant telomerase inhibition, after 72 hours (MCF-7 and NCI H-460; 81.52% and 74.69% reduction, respectively, compared to control). The IC50 of pterostilbene for anti-proliferative activity in MCF7 and NCI H-460 cell lines were found to be 30.0 and 47.2 µM, respectively. The best antimitotic activity was obtained with 80 μM of pterostilbene (100% reduction in water imbibition). All the above results were comparable to that of curcumin. The drug-related properties of pterostilbene were calculated using Molinspiration, Osiris Property Explorer and ACD/Chemsketch softwares. Pterostilbene obeyed Lipinskis Rule of Five indicating its therapeutic potential in humans. It was found that the telomerase inhibitory activity exhibited by pterostilbene was dependent of the cell viability and has the potential to be a new drug candidate against breast and lung cancers.

Evaluation of serum human telomerase reverse transcriptase as a novel marker for cervical cancer.

Human telomerase reverse transcriptase (hTERT) is the catalytic subunit of human telomerase and its rate-limiting component. The purpose of the present study was to investigate the diagnostic value of hTERT in serum of cervical cancer patients. Preoperative values of hTERT, squamous cell carcinoma antigen (SCC-ag) and cancer antigen 125 (CA 125) were measured by enzyme-linked immunosorbent assay (ELISA) in 192 patients with squamous cell carcinoma or adenocarcinoma of the uterine cervix and 38 healthy controls. Elevated pretreatment levels of hTERT were identified in 80.2% of squamous cell carcinoma and 73.8% of adenocarcinoma patients. The expression of serum hTERT was correlated with telomerase activity in cancer tissues of both histological types. Pretreatment serum hTERT levels showed a significant correlation with clinical stage, tumor size and lymph node metastasis, but not with age. Serum hTERT measurement was found to be useful in the diagnosis and assessment of clinical stage of cervical cancer, and to be superior to the conventional tumor markers. Therefore, serum hTERT is a novel and readily available marker for cervical malignancies.

Antioxidant and Analgesic Activities of Pterocarpus marsupium Roxb

The methanolic extract of the bark of Pterocarpus marsupium Roxb. (Papilionaceae) was screened for antioxidant activity in vitro and analgesic activity in mice, respectively. The in vitro antioxidant activity of the bark extract was evaluated using the 1,1-diphenyl-2-picrylhydrazyl assay, and the results were expressed as IC50. Ascorbic acid, used as a standard, had an IC50 = 34.0 μg mL−1, whereas the bark extract of P. marsupium had an IC50 = 53.0 μg mL−1. Use of the hot-plate method to study central analgesic activity of the bark extract in mice indicated that the bark extract of P. marsupium possesses the ability to significantly reduce pain threshold and also increase the response latency period to thermal stimuli in mice, similar to the reference drug pentazocine. The reaction time of mice was significantly increased to 2 hr with 500 mg mL−1 of bark extract, whereas pentazocine also increased reaction time to 2 hr with 5 mg kg−1. A decline in the reaction time beyond 3 hr was observed by the reference drug and bark extract.

Assessment of pulmonary toxicity of MgO nanoparticles in rats.

In this study, we have evaluated the pulmonary toxicity of MgO nanoparticles (MgO NPs) in rats following their exposure. NPs in phosphate buffered saline + 1% Tween 80 were exposed via intratracheal instillation at a doses of 1 mg/kg or 5 mg/kg into rat lungs and evaluated for various tissue damage markers like alkaline phosphatase (ALP) and lactate dehydrogenase (LDH) in bronchoalveolar lavage (BAL) fluid and histopathology of lungs at 1, 7, and 30 days of post‐exposure intervals. A dose‐dependant increase in ALP and LDH activity was observed in BAL fluids of rat lungs than sham control at all post‐exposure periods (P <0.05), and a dose‐dependant infiltration of interstitial lymphocytes, peribronchiolar lymphocytic infiltration, and dilated and/or congested vessels at 1 day post‐exposure period, worsened at 1 week period, and were reduced at 1 month at histology, indicating the pulmonary toxicity of MgO NPs. In conclusion, MgO NPs exposure produced a dose‐dependent pulmonary toxicity in rats and was comparable with that of Quartz particles.

Serum human telomerase reverse transcriptase: a novel biomarker for breast cancer diagnosis.

BackgroundTelomerase is a ribonucleoprotein complex composed mainly of a reverse transcriptase catalytic subunit, telomerase reverse transcriptase (hTERT). Expression of hTERT confers telomerase activity, indicating that hTERT is the rate-limiting component of human telomerase. The aim of the present study was to investigate the diagnostic implications of hTERT in the serum of breast cancer patients.MethodsThe study was conducted on 159 breast cancer patients and 41 healthy volunteers as controls. The evaluation of hTERT, cancer antigen 15.3 and carcinoembryonic antigen were performed by enzyme-linked immunosorbent assay, and analysed for their correlation with the patient’s clinicopathological features.Results27 of 52 (51.9%) patients with stage I breast cancer, 31 of 40 (77.5%) with stage II and 30 of 34 (88.2%) patients with stage III exhibited elevated hTERT levels. Serum hTERT levels showed significantly higher mean values in patients with breast cancer than healthy individuals. The sensitivity and specificity of hTERT in cancer diagnosis was 68.9 and 83.3%, respectively, which is significantly higher than conventional markers. The expression of serum hTERT was significantly correlated with telomerase activity in breast cancer tissues. Pretreatment serum hTERT levels showed a significant correlation with clinical stage, while correlation with nodal status and tumor size were marginal and no correlation was found with family history and age.ConclusionSerum hTERT is useful for diagnosing and assessing the clinical stage of breast cancer and is superior to conventional markers. Therefore, serum hTERT could have a potential application as a novel biomarker for breast cancer diagnosis.

Synthesis and in vitro cytotoxic activity of novel coumarinylimidazo[2,1-b]thiazole derivatives

A series of novel coumarinylimidazo[2,1-b]thiazole derivatives were synthesized by the treatment of 3-(2-aminothiazol-4-yl)-2H-chromen-2-one with phenacyl bromides followed by Vilsmeier–Haack and Knoevenagel condensation reactions. Structures of all the newly synthesized compounds were confirmed by their spectral and analytical studies. All the synthesized compounds were screened for their in vitro cytotoxic activity against Breast cancer cell line (MCF-7), Hepatocellular liver carcinoma cell line (HepG2), Cervical carcinoma cell line (HeLa) and Lung cancer cell line (NCI-H460). Cytotoxic activity results revealed that, the compound 4d has shown broad spectrum activity against MCF-7, HepG2 & HeLa with IC50 values 16.99 ± 0.7, 13.92 ± 0.2 & 5.18 ± 0.1 μM respectively. Compound 6 against MCF-7 (IC50 10.83 ± 0.5 μM) and HeLa (IC50 6.77 ± 0.2 μM), 4a, 4c & 5a against HeLa and 5c against NCI-H460 with IC50 values 7.13 ± 0.4, 14.21 ± 0.6, 17.87 ± 0.5 & 16.27 ± 0.5 μM respectively have shown good activity. Remaining compounds have shown moderate activity against all the tested cell lines.

In Vitro HIV Type-1 Reverse Transcriptase Inhibitory Activity from Leaf Extracts of Scoparia dulcis L.

Aqueous and methanolic crude extracts of Scoparia dulcis L. leaves were screened for activity against human immunodeficiency virus (HIV) type-1 reverse transcriptase (RT) activity. The results were expressed as IC50. Zidovudine, which was used as a standard drug, showed an IC50 of 38.0 μg mL−1, whereas the aqueous and methanolic extracts from leaves of S. dulcis showed an IC50 of 60.0 and 47.0 μg mL−1, respectively. In this study, methanolic extract of S. dulcis leaves showed remarkable HIV type-1 reverse transcriptase inhibitory activity comparable to that of a standard such as zidovudine. Observed results using standardized parameters indicated that S. dulcis has promising HIV type-1 reverse transcriptase inhibitory activity.