Dalton's Lymphoma Ascites Research Articles

Synthesis of coumarin heterocyclic derivatives with antioxidant activity and in vitro cytotoxic activity against tumour cells

The aim of the present work was to synthesise coumarinyl heterocycles and to elucidate the potential role of these compounds as antioxidants and cytotoxic agents against Dalton's lymphoma ascites tumour cells (DLA) and Ehrlich ascites carcinoma cells (EAC). The synthesis of coumarin derivatives containing pyrazole, pyrazolone, thiazolidin-4-one, 5-carboxymethyl-4-thiazolidinone and 3-acetyl-1,3,4-oxadiazole ring is reported. 4-Methylcoumarinyl-7-oxyacetic acid hydrazide (1) reacted with arylazopropanes or hydrazono-3-oxobutyrate derivatives to form pyrazole (3a-c) and pyrazolone derivatives (5a-c). Heterocyclisation of Schiff's bases of 1 with thioglycolic acid, thiomalic acid or acetic anhydride afforded novel heterocyclic derivatives 4-thiazolidinones (7a-c), 5-carboxymethyl-4-thiazolidinones (8a-c) and oxadiazoles (9a-c), respectively. Some of the compounds showed promising antioxidant activity in vitro and cytotoxic activity against DLA cells and EAC cells.

Antitumor and antimicrobial activities and inhibition of in-vitro lipid peroxidation by Dendrobium nobile.

The aim of the study was to determine the antitumor and antimicrobial activities as well as the inhibition of in vitro lipid peroxidation evoked by Dendrobium nobile. Antimicrobial activity of different solvent extracts of flowers and stem of D. nobile against Escherichia coli, Bacillus subtilis, Proteus, Salmonella typhi and Staphylococcus aureus were analyzed separately. The swiss albino mice were induced with Dalton’s Lymphoma Ascites (DLA) cell lines and the antitumor effect of D. nobile was studied by administering orally the aqueous extracts of the flowers of D. nobile. The antitumor activity was measured in DLA cell line induced mice. Inhibition of in vitro lipid peroxidation activity of the D. nobile in both liver homogenate and RBC ghosts was also carried out. The aqueous extracts of stem and flower of D. nobile showed better zone of bacterial inhibition than that of ethanol and chloroform extracts. The plant extracts treated DLA cell induced mice showed better tumor regression, and the flowers of the plant inhibited the in vitro lipid peroxidation, significantly. The present work indicates that the D. nobile flower extracts possessed antimicrobial and antitumor properties in addition to antiperoxidative activity.

Phyllanthus amarus Inhibits Cell Growth and Induces Apoptosis in Dalton's Lymphoma Ascites Cells Through Activation of Caspase-3 and Downregulation of Bcl-2

The authors found in an earlier study that Phyllanthus amarus extract could significantly inhibit the solid and ascites tumor development in mice induced by Dalton's lymphoma ascites (DLA) cells. In the present study, the apoptotic effects of P. amarus against DLA cells in culture was evaluated. P. amarus produced significant reduction in cell viability as determined by the MTT assay. It also induces the formation of apoptotic bodies with characteristic features like plasma membrane invagination, elongation, fragmentation, and chromatin condensation. P. amarus at concentrations of 100 and 200 microg/mL is shown to induce DNA fragmentation. Gene expression analysis reveals that P. amarus induces the expression of caspase-3 and inhibits the expression of Bcl-2, which is an antiapoptotic protein. So the present study provides some insights into the possible mechanism by which P. amarus brings about apoptosis and growth inhibition in DLA cells.

A novel protein fraction from Sesbania grandiflora shows potential anticancer and chemopreventive efficacy, in vitro and in vivo

We report mechanism-based evidence for the anticancer efficacy of a protein fraction, SF2 (Sesbania fraction 2) isolated from the flower of the medicinal plant, Sesbania grandiflora (S. grandiflora). The fraction was evaluated in two murine ascites tumour cell lines and human cancer cell lines of different origin for its anticancer effect. SF2 inhibited cell proliferation and induced apoptosis as demonstrated by DNA fragmentation and externalization of phosphatidyl serine in Daltons lymphoma ascites (DLA) and colon cancer cells (SW-480). Sensitivity to SF2 in these cells was associated with activation of caspases 3, 8 and 9, poly (ADP-ribose) polymerase cleavage and cytochrome C release which attests apoptosis induced cell death. Mechanistically, SF2 down-regulated phorbol myristate acetate (PMA) induced NF-κB, a transcription factor which controls the expression of genes encoding proteins involved in cell regulation and growth control. Additionally, SF2 also down-regulated anti-apoptotic factors such as Bcl-2, p-Akt and cyclooxygenase-2 induced by the tumour promoter PMA suggestive of a possible explanation for its anticancer effect. In vivo studies using ascites and solid tumour models strongly support in vitro findings as SF2 administration increased the life span and decreased the tumour volume in mice bearing tumour. In vivo toxicological evaluation revealed the pharmacological safety of SF2 and may serve as a potential anticancer drug candidate.

Synthesis, Cytotoxic and Antimicrobial Screening of a Proline-Rich Cyclopolypeptide

Present study describes the first total synthesis of a cyclic heptapeptide, stylisin 1 (8) via coupling of tetrapeptide Boc-L-tyrosinyl-L-prolyl-L-leucyl-L-proline-OH and tripeptide L-phenylalanyl-L-isoleucyl-L-proline-OMe followed by cyclization of linear heptapeptide segment. Structure elucidation of synthesized cyclopeptide was done on basis of detailed spectral as well as elemental analysis. From the results of pharmacological screening, it was concluded that cyclopeptide 8 possessed moderate cytotoxicity against Dalton's lymphoma ascites (DLA) and Ehrlich's ascites carcinoma (EAC) cell lines with IC(50) (inhibitory concentration, 50%) values of 10.6 and 14.6 microM. Furthermore, cyclopeptide 8 exhibited moderate to good antimicrobial activity against Gram -ve (negative) bacteria Klebsiella pneumoniae and Pseudomonas aeruginosa, dermatophytes and Candida albicans with minimum inhibitory concentration (MIC) of 6 microg/ml.

Anti-tumor activity of four Ayurvedic herbs in Dalton lymphoma ascites bearing mice and their short-term in vitro cytotoxicity on DLA-cell-line.

The anti-tumor activity and chemopreventive potential of four Ayurvedic herbs viz. Curcuma longa L., Ocimum sanctum L., Tinospora cordifolia (Wild) Miers ex Hook.f & Thomas and Zizyphus mauritiana Lam. were evaluated using Dalton Lymphoma ascites (DLA) tumor model in Swiss Albino mice. The outcome was assessed using survival time, peritoneal ascitic fluid (Tumor volume) and hematological indices as parameters. Animals were divided into five groups (n = 6) viz. one DLA control and four Herb + DLA treated groups. All the four herb + DLA groups were pre-treated with respective herbs for 7 days and hematological indices were measured for entire five groups. On day-8 animals were inoculated with 1x10(6) DLA cells i.p., and Herb + DLA groups were continued with oral herbal treatment for 21-days. Hematological parameters and tumor volume were assessed to find the effects of herbs. Short term in vitro cytotoxicity was determined by Trypan Blue exclusion method and LDH leakage assay using different concentrations of herbal extracts and 5-FU as a positive control and IC(50) for each herbal extract and 5-FU were determined. Oral administration of crude herb increased the survival time and decreased the peritoneal ascitic fluid content significantly. Hb, RBCs and total WBC which were altered by DLA inoculation were restored significantly by all the herbs except O. sanctum. All the four herbs showed in vitro cytotoxic activity against DLA cell-line. Moreover inter group comparison of all the four herbs for anti-tumor activity showed efficacy in the following order--T. cordifolia > Z. mauritiana > or = C. longa > O. sanctum respectively.

Synthesis and in vitro cytotoxic activity of a natural peptide of plant origin

Present work reports the first total synthesis of a phenylalanine and glycine-rich cyclopolypeptide podacycline B by coupling of tripeptide Boc-L-phe-gly-L-phe-OH and tetrapeptide L-ala-gly-L-thr-L-ile-OMe followed by cyclization of linear heptapeptide segment. The chemical structure of the compound was elucidated by FTIR, 1H NMR, 13C NMR, FAB MS spectral data and elemental analyses. The newly synthesized peptide was subjected to biological screening and found to possess high cytotoxicity against Dalton’s lymphoma ascites (DLA) and Ehrlich’s ascites carcinoma (EAC) cell lines with IC50 values of 13.2 and 15.5 μM, in addition to moderate anthelmintic activity against earthworms M. konkanensis, P. corethruses and Eudrilus sp. at a dose of 2 mg ml−1.

Inhibitory effect of Abrus abrin-derived peptide fraction against Dalton's lymphoma ascites model

Peptides derived from larger molecules that are important modulators in cancer regression are becoming leads for development of therapeutic drugs. It has been reported that Abrus abrin, isolated from the seeds of Abrus precatorius, showed in vitro and in vivo antitumor properties by the induction of apoptosis. The present study was designed to evaluate the in vivo therapeutic effectiveness of abrin-derived peptide (ABP) fraction in Dalton's lymphoma (DL) mice model. The lethal dose (LD(50)) of ABP was found to be 2.25 mg/kg body weight and further the acute toxicity was determined with sublethal doses in normal mice. The acute toxicity like body weight, peripheral blood cell count, lympho-hematological and biochemical parameters remained unaffected till 200 microg/kg body weight of ABP. The sublethal doses of ABP showed very significant growth inhibitory properties in vivo DL mice model. There were 24%, 70.8% and 89.7% reductions in DL cell survival in 25, 50 and 100 microg/kg body weight of ABP, respectively. Analysis of the growth inhibitory mechanism in DL cells revealed nuclear fragmentation, and condensation with the appearance of the sub-G(0)/G(1) peak is indicative of apoptosis. Further, the Western blotting showed that apoptosis was mediated by the reduction in the ratio of Bcl-2 and Bax protein expression, and activation of caspase-3 through the release of cytochrome c in DL cells. Kaplan-Meier survival analysis showed an effective antitumor response (104.6 increase in life span (ILS) %) with a dose of 100 microg/kg body weight.

Synthetic and biological studies on a cyclopolypeptide of plant origin

A natural cyclic peptide previously isolated from Citrus medica was synthesized by coupling of tetrapeptide units Boc-Leu-Pro-Trp-Leu-OMe and Boc-Ile-Ala-Ala-Gly-OMe after proper deprotection at carboxyl and amino terminals followed by cyclization of linear octapeptide segment. Solution phase technique was adopted for the synthesis of cyclooctapeptide-sarcodactylamide. Required tetrapeptide units were prepared by coupling of Boc-protected dipeptides viz. Boc-Leu-Pro-OH and Boc-Ile-Ala-OH with respective dipeptide methyl esters Trp-Leu-OMe and Ala-Gly-OMe. Cyclization of linear octapeptide unit was done by p-nitrophenyl ester method. The structure of synthesized cyclopolypeptide was elucidated by FTIR, 1H NMR, 13C NMR, FABMS spectral data and elemental analysis. The newly synthesized peptide was evaluated for different pharmacological activities including antimicrobial, anthelmintic and cytotoxic activities. Synthesis of sarcodactylamide was accomplished with >78% yield utilizing dicyclohexylcarbodiimide (DCC) as coupling agent. Newly synthesized peptide possessed potent cytotoxic activity against Dalton's lymphoma ascites (DLA) and Ehrlich's ascites carcinoma (EAC) cell lines, in addition to moderate anthelmintic activity against earthworms Megascoplex konkanensis, Pontoscotex corethruses and Eudrilus sp. Moreover, cyclopolypeptide displayed good antimicrobial activity against pathogenic fungi Candida albicans and Gram-negative bacteria Pseudomonas aeruginosa, in comparison to standard drugs griseofulvin and ciprofloxacin. Solution phase technique employing DCC and triethylamine (TEA) as base proved to be effective for the synthesis of natural cyclooctapeptide. N-methyl morpholine (NMM) was found to be a better base for the cyclization of linear octapeptide unit in comparison to TEA and pyridine.

A polyherbal ayurvedic drug – Indukantha Ghritha as an adjuvant to cancer chemotherapy via immunomodulation

Indukantha Ghritha (IG) is a polyherbal preparation consisting of 17 plant components widely prescribed by ayurvedic physicians for various ailments. Though it is a known ayurvedic drug, no attempt has been made to scientifically validate its mechanism of action. Preliminary studies in our laboratory showed IG to possess considerable immunomodulatory effects with a Th1 type of immune response. In this regard, we attempted to elucidate its role as an adjuvant to cancer chemotherapy. BALB/c mice were administered IG, for a period of 14 days and parameters such as Hb, total and differential WBC count, bone marrow cellularity, lymphocyte proliferation and function, macrophage phagocytosis and tumor remission were studied. Administration of IG could inhibit tumor development in mice challenged with Dalton's lymphoma ascites. IG-induced leukopoiesis and enhanced median survival time as well as life span in tumor bearing animals. Macrophage phagocytic capacity was also elevated. Flow cytometric analysis of lymphocyte subsets and MTS [3-(4,5-dimethylthiazol-2-yl)-5-(3-carboxymethoxyphenyl)-2-(4-sulphophenyl)-2H-tetrazolium salt] assay for lymphocyte proliferation, yielded promising results which reinforces its use as an adjuvant to cancer chemotherapy. The polyherbal drug could reverse cyclophosphamide-induced myelosuppression in control tumor bearing animals significantly to values near or above normal levels. These results demonstrate the potential of IG, especially in several immunosuppressed conditions and patients suffering from leukopenia as a consequence of cancer chemotherapy.

Queuine promotes antioxidant defence system by activating cellular antioxidant enzyme activities in cancer

Constant generation of Reactive oxygen species (ROS) during normal cellular metabolism of an organism is generally balanced by similar rate of consumption by antioxidants. Imbalance between ROS production and antioxidant defense results in increased level of ROS causing oxidative stress which leads to promotion of malignancy. Queuine is a hyper modified base analogue of guanine, found at first anti-codon position of Q- family of tRNAs. These tRNAs are completely modified with respect to queuosine in terminally differentiated somatic cells, however hypomodification of Q-tRNAs is close association with cell proliferation. Q-tRNA modification is essential for normal development, differentiation and cellular functions. Queuine is a nutrient factor to eukaryotes. It is found to promote cellular antioxidant defense system and inhibit tumorigenesis. The activities of antioxidant enzymes like catalase, SOD, glutathione peroxidase and glutathione reductase are found to be low in Dalton's lymphoma ascites transplanted (DLAT) mouse liver compared to normal. However, exogenous administration of queuine to DLAT mouse improves the activities of antioxidant enzymes. The results suggest that queuine promotes antioxidant defense system by increasing antioxidant enzyme activities and in turn inhibits oxidative stress and tumorigenesis.

Regulation of Caspase‐3 and Bcl‐2 Expression in Dalton′s Lymphoma Ascites Cells by Abrin

The role of abrin, a toxic lectin isolated from seeds of Abrus precatorius Linn in inducing apoptosis in murine Dalton's Lymphoma Ascites (DLA) cells was evaluated. Abrin when incubated at the concentration of 10 ng per million DLA cells could bring about cell death as typical morphological changes with apoptosis. However, necrotic cell death dominated when a higher dose of abrin was used. DNA samples, isolated from DLA cells treated with abrin showed fragmentation. Abrin brought about induction of apoptosis by stimulating the expression of pro-apoptotic Caspase-3, at the same time blocking the expression of Bcl-2, which is an anti apoptotic gene. However, the expression of tumor suppressor gene p53 has not been observed in control and abrin-treated DLA cells. Results suggested that abrin effectively induced apoptotic changes in the tumor cells that led to cellular death.

Pressure Sensitive Adhesive for 6‐Mercaptopurine Transdermal Delivery for Solid Tumor in Mice

The aim of the present study was to develop and characterize the physiochemical properties of transdermal patches of 6‐Mercaptopturine (6‐MP) and evaluate the cytotoxicity, antitumor activity in Balb/c mice using Dalton's lymphoma ascites (DLA) as model cell lines, skin irritation and sensitization in mice and human subjects. 6‐MP was loaded into the patches according to pharmacokinetics properties of 6‐MP. Cytotoxicity was measured by exposing cell suspension to an increased concentration of drug from 50‐1000 ng/ml and the viable cell count was measured by the tryphan blue exclusion method. Results confirmed that 1000 ng/ml of 6‐MP was cytotoxic, and there was an increase in the life span (%ILS) by 71.0% with maximum survival time of 36±1days for 6‐MP transdermal patches, results were statistically significant (p <0.05) compared to untreated control, and anti‐tumor activity was very effective compared to the oral route. Patches did not show any sign of erythema, vesiculations or bullaous reaction, the mean cumulative skin irritation and adherence scoring for both animals and humans proved no irritation sensitization reaction scores were 0 and less than 1, good adherence was seen with score=0, with complete adherence to skin, without leaving any adhesive on skin with score=0 in human subjects. Transdermal patches showed 100% flatness, thickness 150±0.03 mm, good content uniformity, folding endurance (>500 foldings), tensile strength was 2.1 to 7.2 Newton's, elongation was 3–5%, patches were stylish, smooth, transparent, and flexible in appearance. The thumb tack test showed good adhesion, Velcro® protection jackets were suitable for study and served our purpose for licking, scratched and rubbing of applied patches.

Synthetic and Biological Studies on Natural Cyclic Heptapeptide: Segetalin E

Present investigation describes the first total synthesis of a proline-rich cyclic peptide segetalin E (8) by solution phase technique. The chemical structure of the compound was elucidated by FT-IR, 1H-NMR, 13C-NMR, FAB-MS spectral data and elemental analyses. The newly synthesized peptide was subjected to pharmacological screening and found to exhibit high cytotoxicity against Dalton's lymphoma ascites (DLA) and Ehrlich's ascites carcinoma (EAC) cell lines with IC50 values of 3.71 and 9.11 microM, in addition to good anthelmintic activity against earthworms M. konkanensis and P. corethruses at a dose of 2 mg/mL.

Dynamized preparations in cell culture.

Although reports on the efficacy of homeopathic medicines in animal models are limited, there are even fewer reports on the in vitro action of these dynamized preparations. We have evaluated the cytotoxic activity of 30C and 200C potencies of ten dynamized medicines against Dalton's Lymphoma Ascites, Ehrlich's Ascites Carcinoma, lung fibroblast (L929) and Chinese Hamster Ovary (CHO) cell lines and compared activity with their mother tinctures during short-term and long-term cell culture. The effect of dynamized medicines to induce apoptosis was also evaluated and we studied how dynamized medicines affected genes expressed during apoptosis. Mother tinctures as well as some dynamized medicines showed significant cytotoxicity to cells during short and long-term incubation. Potentiated alcohol control did not produce any cytotoxicity at concentrations studied. The dynamized medicines were found to inhibit CHO cell colony formation and thymidine uptake in L929 cells and those of Thuja, Hydrastis and Carcinosinum were found to induce apoptosis in DLA cells. Moreover, dynamized Carcinosinum was found to induce the expression of p53 while dynamized Thuja produced characteristic laddering pattern in agarose gel electrophoresis of DNA. These results indicate that dynamized medicines possess cytotoxic as well as apoptosis-inducing properties.

SYNTHESIS, CHARACTERIZATION AND BIOLOGICAL EVALUATION OF A GLYCINE-RICH PEPTIDE - CHERIMOLACYCLOPEPTIDE E

ABSTRACT The synthesis of a natural cyclic peptide cherimolacyclopeptide E (12) by coupling of tripeptide units Boc-gly-leu-gly-OCH 3 (9) and Boc-phe-tyr-pro-OCH 3 (10) after proper deprotection at carboxyl and amino terminals followed by cyclization of linear hexapeptide segment, is described. Structure elucidation of the cyclopeptide 12 is based on detailed spectral analysis such as FTIR, 1 H NMR, 13 C NMR, FAB MS and elemental analysis. After biological screening, the newly synthesized peptide exhibited high cytotoxicity against Dalton’s lymphoma ascites (DLA) and Ehrlich’s ascites carcinoma (EAC) cell lines with CTC 50 values of 2.76 and 4.96 μM, and potent antimicrobial activity against pathogenic microbes P. aeruginosa, E.coli and C. albicans with MICs between 12.5-6 μg/mL. Furthermore, compound 12 possessed moderate anthelmintic activity against earthworms M. konkanensis, P. corethruses and Eudrilus sp. at 2 mg/mL dose level. Keywords: cherimolacyclopeptide E, cyclic hexapeptide, cytotoxicity, antimicrobial evaluation, anthelmintic activity Corresponding author:e-mail: rajivdahiya04@yahoo.co.in

Immunomodulatory and anti-tumor activities of native and heat denatured Abrus agglutinin

Abrus agglutinin (AAG), a hetero tetrameric gal β (1–3) NAc gal specific lectin, is isolated from seeds of Abrus precatorius. In our previous studies we found that the protein could act as an immunomodulator and immunoadjuvant in native (NA) and heat denatured (HDA) conditions. An anticancer effect of the lectin is reported, but its mode of action is not clearly known. In the present study, the anti-tumor activity of AAG (NA, HDA) has been evaluated in a murine Dalton's lymphoma (DL) ascites tumorogenic model. We found that treatment with both NA and HDA were able to decrease the tumor cell number in vivo and significantly increased median survival time. In vitro studies showed that AAG (NA, HDA) treatment of Dalton's lymphoma ascites cells (DLAC) resulted in growth inhibition at the concentration of 1 μg/ml and above. Whereas, AAG (NA, HDA) at much lower concentrations (∼1 ng/ml) can stimulate peritoneal macrophage and spleen derived NK cells in vitro demonstrating cytotoxicity against DLAC. Cell cycle analysis showed an increased number of cells in Sub-G 0/G 1 phase for in vitro and in vivo treatments. In summary, AAG (NA, HDA) at non-toxic concentration was able to elicit anti-tumor effects in DL bearing mice by stimulating the innate immune system and Th1 type immunomodulation.

Cytotoxicity, Anti-tumor Activity, Cumulative Skin Irritation and Sensitization Study of 5-Fluorouracil from a Transdermal Patch for Dalton's Lymphoma Ascites Cells

Dalton’s lymphoma ascites (DLA) cells were used as a model cell line to evaluate the cytotoxic concentration and anti-tumor activity of 5-fluorouracil (5-FU) through transdermal drug delivery (TDD) for solid tumors. Cytotoxicity was measured by exposing cell suspensions to increased concentrations of drug from 10–50µg/ml and then th ev iable cells count was measured by the tryphan blue exclusion method. The results confirmed that 50µg/ml of 5-FU was cytotoxic to DLA cells. The tumor volume was 0.23 cm 2 and the increase in life span (ILS) was 81.8% with a maximum survival time of 39.5±1.87 days fo r5 -F Um onolithic matrix transdermal patch in mice with solid tumors induced by DLA. The results were significantly different (p 500 foldings), elegance, smoothness, transparency, and flexibility. The Velcro protection jackets were suitable for the study and prevented the mice from licking, scratching, and rubbing the patches.

Antitumor Activity and Antioxidant Status of the Methanol Extract of Careya arborea Bark Against Dalton’s Lymphoma Ascites-Induced Ascitic and Solid Tumor in Mice

Based on the ethnomedical use of Careya arborea Roxb bark in the treatment of tumors, the present study was carried out to evaluate the anticancer potentials against Dalton’s lymphoma ascites (DLA)-induced ascitic and solid tumors. The methanol extract of its bark given orally to mice at the dose of 250 or 500 mg/kg body weight for 10 days caused significant reduction in percent increase in body weight, packed cell volume, and viable tumor cell count when compared to the mice of the DLA control group. Restoration of hematological and biochemical parameters towards normal was also observed. Histological observations of liver and kidney also indicated repair of tissue damage caused by tumor inoculation. The extract at the dose of 5 or 25 mg/kg body weight given i.p. daily for 14 days significantly reduced the solid tumor volume induced by DLA cells.

Synthetic studies on novel benzimidazolopeptides with antimicrobial, cytotoxic and anthelmintic potential

Four substituted benzimidazolyl-benzoic/salicylic acids 5-8 were synthesized by interaction of 5,6-dimethyl-/6-nitrobenzimidazoles with diazotized substituted/unsubstituted aminobenzoic acids in the presence of cupric chloride. The coupling of compounds 5-8 with different amino acid ester hydrochlorides/dipeptide/tripeptide/tetrapeptide methyl esters afforded novel benzimidazolopeptide derivatives 5a-f, 6a-h, 7a-g and 8a-g. The structures of all newly synthesized compounds were established on the basis of analytical, IR, (1)H NMR, (13)C NMR and mass spectral data. Selected peptide ester derivatives were further hydrolyzed by using lithium hydroxide (LiOH) to yield corresponding acid derivatives 5b(a)-d(a), 6e(a)-g(a), 7c(a)-e(a) and 8e(a)-g(a). All peptide derivatives were screened for their antimicrobial, anthelmintic and cytotoxic activities. Almost all newly synthesized benzimidazolopeptides have shown moderate to good anthelmintic activity against all three earthworm species and good antimicrobial activity against pathogenic fungal strains Candida albicans and Aspergillus niger, gram negative bacterial strains Pseudomonas aeruginosa and Escherichia coli. Compounds 8g and 8g(a) possessed significant cytotoxic activity against Dalton's lymphoma ascites (DLA) and Ehrlich's ascites carcinoma (EAC) cell lines.