Good Cytotoxic Activity Research Articles

Synthesis of novel 3-arylated 2-hydroxy-1,4-naphthoquinone derivatives via microwave-assisted three-component domino reaction and evaluation of their cytotoxic activity

Synthesis of novel 3-arylated 2-hydroxy-1,4-naphthoquinone derivatives via microwave-assisted three-component reaction starting from 2-hydroxy-1,4-naphthoquinone, tetronic acid, and various aromatic aldehydes has been described. This multicomponent domino reaction proceeded through the Knoevenagel condensation, Michael addition, deprotonation, and 1,3-H shift steps. Five of the synthesized compounds displayed good cytotoxic activity against two human cancer cell lines, KB and HepG2, with half maximal inhibitory concentration values in a range of 4–20 μM.

Bioassisted Synthesis of Gold Nanoparticles from Saccharomonospora glauca: Toxicity and Biocompatibility Study

Bionanosynthesis is an important aspect in the rapidly growing field of nanotechnology that provides a good functional material of biological interest. In the present study, bioassisted synthesis of gold nanoparticles (GNPs) was carried out using Saccharomonospora glauca, rare actinomycetes isolated from soil and were tested for haemocompatibility and cytotoxicity against NIH3T3, HT-29, and Hep 2 cells. Bioreduction was monitored by using UV-visible spectroscopy and characterised by FTIR, XRD, SEM, DLS and zeta potential. XRD confirmed the crystalline nature of the synthesised GNPs. The average particle size obtained by SEM and DLS was found to be 30 nm with spherical in shape. The synthesised GNPs showed good cytotoxic activity against cancer cell lines HT-29 and Hep 2 with an IC-50 value of 49.8 μg/ml and 96.8 μg/ml respectively and least toxicity for normal cell lines NIH3T3. This was further confirmed by staining the cells with AO and PI dual staining for apoptosis detection. The synthesised GNPs showed excellent biocompatibility for human blood without haemolysis. The work reports for the first time the synthesis of simple and eco-friendly GNPs from Saccharomonospora glauca showing excellent biocompatibility and good toxicity for cancer cells with mild toxicity for normal cell lines that can be implemented for biomedicine.

Synthesis, DNA binding, antibacterial and anticancer properties of two novel water-soluble copper(II) complexes containing gluconate.

In this paper, two new Cu(II) complexes, [Cu(Gluc)(HPB)(H2O)]Gluc (CuG1) and [Cu(Gluc)(HPBC)(H2O)]Gluc (CuG2) (where HPB=2-(2'-pyridyl)benzimidazole, HPBC=5-chloro-2-(2'-pyridyl)benzimidazole, Gluc=d-Gluconic acid), with good water solubility were synthesized and characterized. These complexes exhibited a five-coordinated tetragonal pyramidal geometry. The DNA binding and cleavage properties of the complexes were investigated using multi-spectroscopy, viscosity measurement, molecular docking and gel electrophoresis analysis methods. The results showed that the complexes could interact with DNA by insertion and groove binding, and cleave CT-DNA through a singlet oxygen-dependent pathway in the presence of ascorbic acid. The studies on antibacterial and anticancer activities invitro demonstrated that both complexes had good inhibitory activity against three Gram-positive bacteria (Staphylococcus aureus, Bacillus subtilis, Listeria monocytogenes) and one Gram-negative bacterium (Escherichia coli) and good cytotoxic activity toward the tested cancer cells (A549, HeLa and SGC-7901). CuG2 showed higher antimicrobial and cytotoxic activities than CuG1, which was consistent with their binding strength and cleavage ability to DNA, indicating that their antimicrobial and cytotoxic activities may be related to the DNA interaction. Moreover, the cell-based mechanism studies have indicated that CuG1 and CuG2 could arrest the cell cycle at G2/M phase, elevate the levels of intracellular reactive oxygen species (ROS) and decrease the mitochondrial membrane potential (MMP). The results showed that the complexes could induce apoptosis through DNA-damaged and ROS-mediated mitochondrial dysfunction pathways. Finally, the invivo antitumor study revealed that CuG2 inhibited tumor growth by 50.44%, which is better than that of cisplatin (40.94%).

Cytotoxic activity of flavonoid from local plant Eriocaulon cinereum R.B against MCF-7 breast cancer cells.

Eriocaulon cinereum R. Br is used as traditional medicine by the local community in Bangka Belitung Island, Indonesia. The plant is processed as an infusion for fever, boosts the immune system, and treats tumor cells. However, scientific research on this species is still limited. The aims of this study were to determine the cytotoxic of E. cinereum against MCF-7 cells. The results suggested that one of the compounds has a good cytotoxic activity. Therefore, it is quite promising in the effort of cancer drug discovery. The active compound has a flavonoid, which plays a role in several anticancer mechanisms. This study provided scientific evidence regarding the utilization of E. cinereum by the local community for cancer therapy. The plant can be further developed as an alternative agent to treat cancer or as cancer adjuvant therapy.

Dihydronaphthalenone chalconoid derivatives as potential cathepsin B inhibitors; design, synthesis, cytotoxicity evaluation and docking analysis

Cathepsin B, an abundant expressed cysteine peptidase, plays a key role in cancer cell proliferation, tumor metastasis, apoptosis, angiogenesis, invasion and migration. Therefore, development of cathepsin B inhibitors to treat cancer is of great significance. In this study, dihydronaphthalenone chalconoid derivatives containing different benzyliden moieties were synthesized via an efficient route in microwave condition that resulted in the desired compounds in high yields compared to acid- or base-catalyzed refluxing conditions. Cytotoxicity of the compounds was evaluated against K562, HT-29 and MCF-7 human cancer cell lines by MTT assay. P1, P3 and P9 (containing 4-OCH3, 3-NO2 and 4-CN moieties on phenyl ring, respectively) exhibited good cytotoxic activity with an IC50 range of 7.1-28.9 μM. Molecular docking analysis was carried out to investigate the possible interactions and binding modes of all compounds with cathepsin B. The most promising compounds, P1, P3 and P9 were well accommodated within the active site and had the least estimated free binding energies. It was concluded from both MTT assay and docking studies that some dihydronaphthalenone chalconoid derivatives could be suggested as effective cytotoxic agents and potential cathepsin B inhibitors

A REVIEW ON CYTOTOXIC ACTIVITY OF (GARCINIA COWA ROXB.): POTENTIAL AS AN ANTICANCER

Cancer is a disease of abnormal body tissue cells that turn malignant. From the data, it can be seen that new cases and the death rate from cancer continues to increase every year so that efforts are made in the search for new anticancer agents for the prevention and treatment of cancer. There are many natural ingredients that can be used for its benefits, one of which is the Asam Kandis plant (Garcinia cowa Roxb.) This plant is rich in phytochemicals. It can be an important source of natural cytotoxic compounds and has potential as an anticancer. The analysis showed that the extract or compound from the roots, bark, twigs, leaves, and fruit rind of Asam Kandis (Garcinia cowa Roxb.) has good cytotoxic activity and is active against cancer cell lines so that it can help in the development of cancer therapy.

Preparation, COX-2 Inhibition and Anticancer Activity of Sclerotiorin Derivatives.

The latest research has indicated that anti-tumor agents with COX-2 inhibitory activity may benefit their anti-tumor efficiency. A series of sclerotiorin derivatives have been synthesized and screened for their cytotoxic activity against human lung cancer cells A549, breast cancer cells MDA-MB-435 using the MTT method. Among them, compounds 3, 7, 12, 13, 15, 17 showed good cytotoxic activity with IC50 values of 6.39, 9.20, 9.76, 7.75, 9.08, and 8.18 μM, respectively. In addition, all compounds were tested in vitro the COX-2 inhibitory activity. The results disclosed compounds 7, 13, 25 and sclerotiorin showed moderate to good COX-2 inhibition with the inhibitory ratios of 58.7%, 51.1%, 66.1% and 56.1%, respectively. Notably, compound 3 displayed a comparable inhibition ratio (70.6%) to the positive control indomethacin (78.9%). Furthermore, molecular docking was used to rationalize the potential of the sclerotiorin derivatives as COX2 inhibitory agents by predicting their binding energy, binding modes and optimal orientation at the active site of the COX-2. Additionally, the structure-activity relationships (SARS) have been addressed.

Synthesis, in-silico Studies and Evaluation of Anticancer Activity of Some Novel Benzothiazole Substituted 4-Thiazolidinones

Abstract: Background: Cancer is one of the leading diseases associated with the high degree of mortality. In current scenario chemotherapy is the major treatment for cancer and it still has few limitations. The continuous seek for highly effective and safe anticancer agents is the one of the major goal for medicinal chemists. Objectives: In the present work, the hybrid molecule i.e benzothiazole substituted 4-thiazolidinone has been synthesized and evaluated for anticancer activity. Methods: A series of novel benzothiazole substituted 4-thiazolidinone derivatives were synthesized by reacting 2-amino-6-methyl benzothiazole with aromatic aldehydes in alcoholic media, resulting schiff bases are made to react with thioglycolic acid in dioxane. Characterization of synthesized compounds were done by IR, 1H NMR, Mass spectroscopy. In silico studies with molecular docking was performed for the synthesized derivatives by taking proteins from PDB i.e VEGFR-2 kinase and Human thymidylate synthase (PDB ID:2QU5 and 5HS3) as the targets. Results and Discussion: Based on the docking score, best four compounds were selected and screened for in-vitro anticancer activity. From the in-vitro data, finally one potential molecule was selected and evaluated for in-vivo cytotoxic activity. Conclusion: All 4 screened derivatives were found to show good cytotoxic activity, out of which P14 can be considered as promising molecule. Key words: Benzothiazole, 4-Thiazolidinone, Anticancer, In silico, Docking.

Cytotoxicity and chromatographic analysis of Dioon spinulosum, family Zamiaceae

The identification of cytotoxic secondary metabolites from Dioon spinulosum Dyer ex. leaves was our aim. Thus, the evaluation of the cytotoxic activity of the total alcohol extract and successive fractions [n-hexane, dichloromethane (DCM), ethyl acetate, and n-butanol] against endocervix carcinoma (HeLa) and breast cancer (MCF7) cell lines was carried out using the sulforhodamine B assay. Identifying and authenticating D. spinulosum Dyer by DNA fingerprinting were carried out using Start Codon Translation (SCoT) and Inter simple Sequence Repeat, and revealed that SCoT4, SCoT6, SCoT8, HB-9, and HB-14 can be used for the identification of D. spinulosum at the genetic level. Chromatographic analysis and isolation, followed by the spectroscopic detection of the isolated compounds, were achieved by using various spectroscopic techniques. The following five compounds were isolated: β-sitosterol (1), 7,7'',4',4'''-O-tetra-methylamentoflavone (2), sciadopitysin (3), amentoflavone (4), and aromadendrin (5). Compounds 1 and 5 were obtained for the first time from the titled plant. This plant showed good cytotoxic activity against endocervix carcinoma as the total ethanolic extract, n-hexane, DCM, ethyl acetate, and n-butanol fractions showed IC50 values of 21.8, 21.1, 24.5, 26.5, and 21.4 μg/ml respectively, against HeLa cell lines. On the other hand, the total ethanolic extract and the fraction of ethyl acetate showed good anticancer activity against MCF7 cell line with IC50 values of 22.5 and 18 μg/ml, respectively. Aromadendrin showed IC50 = 12.5 μg/ml against MCF7 cell line. In conclusion, aromadendrin may be responsible for D. spinulosum cytotoxicity against breast cancer cell lines. The total extract exhibited a promising adjunctive therapy for anticancer patients with endocervix and breast carcinomas.

Design, Synthesis and Antiproliferative Activity of Novel Heterocycles from 6-Iodo-2-phenyl-4H-benzo[d][1,3]thiazine-4-thione

ABSTRACT The present work is dedicated to utilize the reactivity of 6-iodo-2-phenyl-4H-benzo[d][1,3]thiazine-4-thione to motivate new different heterocyclic systems namely, quinazoline-4(3H)-thione,benzimidazol-2(3H)-one, pyrazole and thiadiazole derivatives which have been structurally characterized with spectroscopic data such as IR, 1HNMR and mass spectra. The synthesized compounds were evaluated for the anticancer activity against HePG-2 and MCF-7 cell lines. 1-(3,5-Dimethyl-1H-pyrazol-1-yl)-2-(6-iodo-2-phenyl-4-thioxoquinazolin-3(4H)-yl)ethanone and ethyl 3-(2-(2-(6-iodo-2-phenyl-4-thioxoquinazolin-3(4H)-yl)acetyl)hydrazono)butanoate showed the highest cytotoxic activities against the two cell lines comparable to that of the reference compound doxorubicin. Most of the synthesized compounds also exhibited good cytotoxic activity.

New pyran derivative with antioxidant and anticancer properties isolated from the probiotic Lactobacillus plantarum H24 strain

This work was aimed to prepare, isolate and identify antioxidant and cytotoxic compound from the culture filtrate of a probiotic lactobacillus strain. New compound, plantarone (1), together with two known compounds, kojic acid (2) and methyl dodecanoate (3), were isolated from the ethyl acetate extract of the culture filtrate of probiotic Lactobacillus plantarum H24. Their structures were elucidated using spectroscopic methods including 2 D NMR, HRMS analyses. Isolated compounds were screened for antioxidant and cytotoxic activities against Caco-2 colon cancer cells. Compounds 1 and 2 showed lowers DPPH radical scavenging activities (p < 0.05) with IC50 values of 66.3 ± 0.34 μM and 50.2 ± 0.28 μM respectively, compared to standard butylated hydroxyanisole (BHA: IC50 = 44.2 ± 0.24 μM). Whereas only compound 1 showed a good cytotoxicity activity with inhibition value of 60.72 ± 3.55%. Accordingly, L. plantarum H24 could be used to prevent oxidative stress and its injuries, improving human health.

Suppressive efficiency of Kojic acid from Aspergillus tamarii MM11 against HepG-2 cell line derived from human liver cancer

Purpose: To evaluate the antioxidant and cytotoxic properties of Kojic acid (KOJIC ACID) from Aspergillus tamarii MM11 against HepG-2 cell line derived from human liver cancer.Methods: The crude extract of A. tamarii MM11 was dissolved in a mixture of CH2Cl2/MeOH (85:15) and separation was done using silica gel chromatography using gradient size exclusion chromatograph. The non-polar oily fractions were subjected to gas chromatography-mass spectrometric (GC-MS) analysis. Kojic acid structure was identified by x-beam crystallography and spectroscopic methods. Total antioxidant properties of KOJIC ACID were evaluated by using 1,1-diphenyl-2- picrylhydrazyl (DPPH) against ascorbic acid as a reference. The cytotoxic activity of KOJIC ACID from A. tamarii MM11 was investigated on the human cell line of liver cancer (HepG-2) using a sulforhodamine B (SRB) assay based on a cell density determination by the measurement of cellular protein content.Result: Highly bioactive Kojic acid was isolated as the main product. A. tamarii MM11 Kojic acid showed good antioxidant activity with half-maximal inhibitory concentration of IC50 at concentrations of 10.34 compared to 6.79 μg/mL for ascorbic acid. Kojic acid also showed good cytotoxic activity against HepG-2 cell line of human liver cancer with IC50 at 6.20 compared to 3.25 μg/mL of reference drug doxorubicin.Conclusion: Kojic acid produced naturally from A. tamarii MM11 shows good antioxidant and cytotoxic activity against HepG-2 cell line derived from human liver cancer. These findings suggest that Kojic acid can be therapeutically used as an antitumor drug after further in vivo studies.&#x0D; Keywords: Aspergillus tamarii, Secondary metabolites, Kojic acid, Anticancer, Liver cancer

Biosynthesis of Hydroxy Citric Acid Mediated Zinc Nanoparticles and Its Antioxidant and Cytotoxic Activity

Aim: To evaluate biosynthesis of hydroxy citric acid mediated zinc nanoparticle and its antioxidant and cytotoxic activity&#x0D; Introduction: Hydroxy citric acid is a chemical that is found in fruit rinds of Garcinia cambogia, Garcinia indica, and Garcinia atroviridis. Hydroxy citric acid is used to improve exercise performance and weight loss. Hydroxy citric acid can cause nausea, digestive tract discomfort, and headache when used short-term. Long-term safety is unknown.Zinc oxide nanoparticles are nanoparticles of zinc oxide that have diameters less than 100 nanometers. Zinc nanoparticles have a large surface area relative to their size and high catalytic activity. The exact physical and chemical properties of zinc oxide nanoparticles depend on the different ways they are synthesized. zinc oxide nanoparticles have also been shown to exhibit strong protein adsorption properties, which can be used to modulate cytotoxicity, metabolism or other cellular responses.&#x0D; Materials and Methods: Evaluation of anti-oxidant was done by DPPH activity and evaluation of cytotoxic activity was done by brine shrimp lethality assay. Colour changes was noted in evaluation of cytotoxic activity&#x0D; Results: The antioxidant activity was exhibited well at higher doses when compared to standard, but there was only 40% of cytotoxicity achieved which indicates its potential.Cytotoxic activity reveals that the drug showed a very good result at a concentration of 25 ul it showed a 40% of lethality thereby showing that Hydroxycitric acid medicated zinc oxide nanoparticles shows a potent activity when compared to that with the standard.&#x0D; Conclusion: The study concludes that hydroxy citric acid shows good antioxidant and cytotoxic activity.

Isomannide monoundecenoate‐based 1,2,3‐triazoles: Design, synthesis, and in vitro bioactive evaluation

AbstractA new series of isomannide monoundecenoate‐based 1,2,3‐triazole analogs 6a–e were designed by employing click chemistry in good yields. in vitro bioactive assay manifested that the several target compounds exhibited promising antibacterial and antifungal activities. Notably, compounds having phenyl substituted triazole 6a, and hydroxy phenyl substituted triazole 6b possessed highly selective promising inhibition towards Gram‐positive bacterial strains namely Bacillus subtilis and Staphylococcus aureus with MIC value of 3.9 μg/mL. Further, these potential hybrids (6a and 6b) also exhibited highly impressive antifungal activity against the tested panel of Candida strains with MIC value of 3.9 μg/mL. Based on our in vitro preliminary antimicrobial study, these two compounds 6a and 6b have been identified as potential antimicrobial lead compounds. Moreover, all prepared derivatives were also evaluated for their in vitro cytotoxic activities against A549, MCF7, DU145 and HeLa cancer cell lines. The results indicated that only the hydroxy phenyl substituted triazole analog 6b displayed good cytotoxic activity towards all tested human cancer cell lines without any significant effects on normal cell line (HUVEC).

The cytotoxicity of brazilin and derivatives might be due to an inhibition of the c-Src-kinase

&lt;p&gt;In this study, several derivatives of brazilin with different lipophilicity were synthesized. The cytotoxic potential of these substances was evaluated in S.R.B. assays. A triacetylated brazilin reaction with PBr&lt;sub&gt;3&lt;/sub&gt; or PCl&lt;sub&gt;3&lt;/sub&gt; and a subsequent aqueous workup led to the formation of a phosphorous ester containing two triacetylated brazilin subunits. This compound held unexpected high cytotoxicity. In this study, Brazilin-derived triacetate showed good cytotoxic activity (EC50 = 5.2 M) concerning A2780 carcinoma cells. The results from docking studies suggest that brazilin's cytotoxicity might be due to an inhibition of a tyrosine kinase in an ATP-competitive manner.&lt;/p&gt;

BIOSYNTHESIS, CHARACTERIZATION, BACTERICIDAL AND TOXIC EFFECT OF SILVER NANOPARTICLES USING Klebsiella pneumoniae STRAIN STC1

Nanotechnology dealt with nanoparticles having a size of 1-100nm used significantly in pharmaceutical science and many other fields. The use of microorganisms in the synthesis of nanoparticles emerged as an eco-friendly method. Klebsiella pneumoniae strain STC1 was isolated from cow’s milk and identified by 16S rRNA sequencing. The biosynthesis was done using the fixed ratio of aqueous solution of the bacterial supernatant and AgNO3 and the colour change was observed which proved the formation of silver nanoparticles. The nanoparticles were characterized by UV-Visible Spectrophotometer, FTIR, XRD and SEM. The nanoparticles were found to have sizes ranging from 15 to 70nm. The antibacterial activity of silver nanoparticles was studied against methicillin resistant Staphylococcus aureus, Clostridium perfringens, Pseudomonas sp. and Proteus sp. The Minimum Inhibitory Concentration of silver nanoparticles was found to be 50µg/ml against methicillin resistant Staphylococcus aureus. The synergistic effect of the silver nanoparticles with commercial antibiotics erythromycin and tetracycline was found to be more evident. The time kill assay and the cytoplasm diffusion assay showed the effectiveness of synthesized silver nanoparticles in the study. The synthesized silver nanoparticles had a great antibacterial potential against methicillin resistant Staphylococcus aureus. The toxic effect of silver nanoparticles revealed that as the concentration of the silver nanoparticles increased, the effect of toxicity increased and the hatching percentage of Artemia cysts decreased. The innovation in this present study is that the biosynthesis of nanoparticles is simple, cost effective, providing good bactericidal and cytotoxic activity and it can represent a future for more therapeutic and pharmacological applications.

Synthesis and Antitumor Activity Evaluation of Cyclometalated 2H-Indazole Ruthenium(II) and Iridium(III) Complexes.

In this work, a series of novel C-N cyclometalated 2H-indazole Ru(II) and Ir(III) complexes were synthesized, wherein chelating ligands with substituents like H, and isopropyl group in the R4 position of the phenyl ring of the 2H-indazole chelating ligand are present. The cytotoxicity of Ru(II) and Ir(III) complexes has been evaluated against different human cancer cell lines (HeLa, MCF-7, and A549) in a concentration-dependent manner. The new iridium complex with isopropyl substituent in the phenyl ring of the 2H-indazole moiety showed good cytotoxic activity against MCF-7 cells with an IC50 value 3.5 μM. The complex also exhibited cytotoxicity comparable to that of cisplatin. The ability of this compound inducing apoptosis was tested by nuclear condensation, cell membrane blebbing and caspase 3/7 activation. Further, this iridium complex is capable of inhibiting cancer cell migration when tested in MCF-7 cell line. Subsequently, we have studied the DNA binding and protein binding ability of the newly synthesized iridium complex.

Cytotoxic and Antioxidant Activity of Zinc Oxide Nanoparticles Synthesised Using Maranta Arundinacea Root Extract

The main aim of this study was to employ Maranta arundinacea root extract in the synthesis of Zinc oxide nanoparticles and check the antioxidant activity and cytotoxic effect. The use of nanotechnology in medicine especially for drug delivery is shown to have numerous benefits. Nanoparticles are being used to lessen toxicity and facet results that capsules may additionally impose on the patient. The zinc oxide nanoparticles synthesized using different plant extract used for many biomedical applications such as anticancer activity, antibacterial activity, antioxidant activity, antifungal activity and many more applications used in medicine ( Diagnosis and drug) Plant mediated organic synthesis of nanoparticles has been gaining importance because of its simplicity and eco friendliness. Maranta arundinacea mediated Zinc oxide nanoparticles were initially synthesised and characterised by UV-Visible spectrophotometer and TEM. Further the Maranta arundinacea mediated ZnoNPs were subjected to DPPH assay to determine the antioxidant activity. Maranta arundinacea mediated ZnoNPs were biosynthesised with ease and showed good antioxidant and cytotoxic activity . This study concludes that Maranta arundinacea mediated ZnoNPs nanoparticles have the potential to be used as an effective antioxidant. Hence, it may be employed in large scale production and may be used in many medicinal applications where there is a need for antioxidant.

SYNTHESIS OF SOME 2,3-DIHYDRO-1,3,4-OXADIAZOLES AND 4,5-DIHYDRO-1,2,4-TRIAZOLES AS ANTICANCER AGENTS

Objective: The main objective of this work was to synthesize and evaluate the novel 2,3-dihydro-1,3,4-oxadiazole and 4,5-dihydro-1,2,4-triazole derivatives for cytotoxic activities.&#x0D; Methods: The 2,3-dihydro-1,3,4-oxadiazole derivatives 4a-h were synthesized by cyclization of N'-(substituted-benzylidene) isonicotinohydrazide 3a-e in refluxing acetic anhydride. The 2,3-dihydro-1,3,4-oxadiazole derivatives 4a-h were converted into the corresponding 4,5-dihydro-1,2,4-triazoles 5a-h using ammonia. All the synthesized compounds were identified, depending on the physical and spectral data. Title compounds were assessed for their cytotoxic activity against human cancer cell line (MCF-7) by using Sulforhodamine B (SRB) colorimetric assay.&#x0D; Results: All the synthesized compounds showed characteristic peaks in FTIR, 1HNMR and Mass spectral analysis. The results of the in vitro cytotoxic activity revealed that the compound 4c exhibited equipotent cytotoxic activity with an IC50 value of 8.04 µM when compared with that of standard drug doxorubicin (IC50= 8.02 µM). The reminder compounds have shown good to moderate cytotoxic activities when compared with that of a reference standard.&#x0D; Conclusion: We synthesized a series of title compounds in quantitative yields. Most derivatives showed moderate to good cytotoxic activity.&#x0D;

Computational Studies of bis-2-Oxoindoline Succinohydrazides and their In Vitro Cytotoxicity.

The discovery of clinically relevant EGFR inhibitors for cancer therapy has proven to be a challenging task. To identify novel and potent EGFR inhibitors, the quantitative structure-activity relationship (QSAR) and molecular docking approach became a very useful and largely widespread technique for drug design. We performed the in vitro cytotoxic activity on HEPG-2 cell line and earlier on MCF-7 and A 549 by using MTT assay method. The development of 3D QSAR model of N1,N4-bis(2-oxoindolin-3- ylidene) succinohydrazides using the stepwise-backward variable methods to generate Multiple Linear Regression method elucidates the structural properties required for EGFR inhibitory activity and also perform the Molecular Docking studies on EGFR (PDB ID:1M17). Further, we analysed for Lipinski's rule of five to evaluate the drug-likeness and established in silico ADMET properties. The resulting cytotoxicity (IC50) values ranged from 9.34 to 100 μM and compared with cisplatin as a standard. Among the series of compounds, 6j showed good cytotoxic activity on HEPG-2 cell line with 9.34 μM, IC50 value. Most of the evaluated compounds showed good antitumor activity on HEPG-2 than MCF-7and A549. The developed 3D QSAR Multiple Linear Regression models are statistically significant with non-cross-validated correlation coefficient r2 = 0.9977, cross-validated correlation coefficient q2 = 0.902 and predicted_r2 = 0.9205. Molecular docking studies on EGFR (PDB ID: 1M17) results, compounds 6d, 6j and 6l showed good dock/PLP scores i.e. -81.28, -73.98 and -75.37, respectively, by interacting with Leu-694, Val-702 and Gly-772 amino acids via hydrophobic and hydrogen bonds with Asn818 and Met- 769. Further, we analysed drug-likeness and established in silico ADMET properties. The results of 3D QSAR studies suggest that the electrostatic and steric descriptors influence the cytotoxic activity of succinohydrazides. From the molecular docking studies, it is evident that hydrophobic, hydrogen and Van Der Waal's interactions determine binding affinities. In addition to this, druglikeness and ADMET properties were analysed. It is evident that there is a correlation between the QSAR and docking results. Compound 6j was found to be too lipophilic due to its dihalo substitution on isatin nucleus, and can act as a lead molecule for further and useful future development of new EGFR Inhibitors.