SR Cell Line Research Articles

The Effective Synthesis of New Benzoquinoline Derivatives as Small Molecules with Anticancer Activity.

In this study, some novel benzo[c]quinoline derivatives were synthesized, their structural characteristics were described, and their in vitro anticancer efficacy was investigated. The synthesis involves an initial quaternization of the nitrogen atom from benzo[c]quinoline and then a [3+2] dipolar cycloaddition reaction of the in situ formed ylide. The effectiveness of synthesis using traditional thermal heating (TH) compared to microwave (MW) and ultrasound (US) irradiation was investigated in detail. The setup of a reaction under MW or US irradiation offers a number of additional benefits: higher yields, a reduction in the amount of solvent used compared to TH, a reduction in the reaction time from hours to minutes, and a reduction in the amount of energy consumed. The structure of all the obtained compounds was proved by several spectral techniques (FTIR, HRMS, and NMR). All benzo[c]quinoline derivatives (quaternary salts and cycloadducts) along with ten other benzo[f]quinoline derivatives (quaternary salts and cycloadducts), previously obtained, were tested in an in vitro single-dose anticancer experiment. The results demonstrated that the cycloadducts 5a-c and 6a-c exhibit stronger anticancer activity than quaternary salts 3a-c. The most active compound is compound 5a, with anticancer activity on most of the cell lines studied, while the second most active compound is 6c, showing significant lethality for the SR leukemia cell line (17%). Structure-activity relationship (SAR) correlations are also included in the study.

Design, synthesis, and evaluation of new benzimidazole‏ ‏‎thiourea ‎derivatives as antitumor agents.

Novel benzimidazole thiourea derivatives were designed and synthesized based on sorafenib as a lead compound. The benzimidazole moiety was traded by the pyridine ring to enhance the hydrophobic interaction and retain hydrogen bonding in the hinge region, while lipophilic moieties with different bulkiness were employed in the deep hydrophobic pocket for better hydrophobic interactions. Thiourea as a urea bioisostere was also utilized. Substantial activity was demonstrated against a leukemia subpanel in an in vitro antitumor screening at the NCI. In the single-dose assay, compounds 7i, 7j, and 7l had a GI%) higher than sorafenib against most leukemia cell lines (GI% = 86.2%-137.1%), while in the five-dose assay, compound 7l outperformed sorafenib against the HL-60(TB) and SR leukemia cell lines in terms of GI50 , TGI, and LC50 . Compound 7l also caused cycle arrest at the G0-G1 and S phases in the HL-60(TB) leukemia cell line and induced apoptosis via elevating the Bax/Bcl-2 ratio and increasing caspases 3, 7, and 9 by 5.1-, 3.2-, and 5.2-fold, respectively. Compounds 7i, 7j, and 7l also inhibited the vascular ‎endothelial growth factor receptor-2 (VEGFR-2), B-Raf(V600E) , and platelet-derived growth factor receptor ‎beta (PDGFR-β) enzymes with an IC50 range of 0.063-0.44 μM. COMPARE analysis and a molecular docking study were also performed to predict the possible mechanism of action and binding mode, respectively.

A Promising Natural Anticancer Compound Derived from Gymnoascus dankaliensis.

Cancer is the uncontrolled growth of malignant cells and is universally estimated to be a common cause of death. No decisive treatment has been identified to cure cancer; therefore, scientists have focused on developing safe and effective treatments. The activity of natural compounds isolated from living organisms, such as fungi, has been investigated in cancer cells. This study aimed to isolate and analyze natural products, as secondary metabolites (SM), of the fungus Gymnoascus dankaliensis (G. dankaliensis) and identify their activity against SR and HCT-18 (HRT-18) cell lines. G. dankaliensiswas isolated from dung samples and identified using a molecular method. The internal transcribed spacer region was amplified from the isolated genomic DNA and sequenced afterward. The isolate was grown on a rice medium as a solid-state fermentation medium to extract natural metabolite products using the ethyl acetate extraction method. The GC-MS analyzed the compound of the natural extract, and the activity of the natural extract was identified against SR and HCT-18 cell lines. The results revealed the ability of G. dankaliensis to produce a natural product as an SM composed of five compounds. The growth of the treated SR and HCT-8 cell lines with the natural extract was inhibited after incubation for 27 h, with the IC50 being 3.57 and 8.61 µg/mL on the HCT-18 and SR cell lines, respectively. In conclusion, the natural extract isolated from the SM of G. dankaliensis showed activity against cancer cells, affecting the SR and HCT-18 cell lines, compared to the control. These results revealed that the product is a promising anticancer treatment.

The Effect of NSAIDS and Oral Hypoglycemic Agent on Leukemia and Lymphoma Cell Lines

Cancer is regarded as global burden and a serious health challenge. Its occurrences increased due to population aging and the prevalence of risk factors. This study investigated the eff ect of metformin and aspirin on two cell lines SR (diff use large B cell lymphoma) and NB4 (promyelocytic leukemia). The eff ect of metformin as monotherapy on SR was 28.43% viable, while on NB4, only 44.4% were viable. However, the eff ect of aspirin on SR and NB4 cell lines were decreased; the percentage of cell viability were 27.2 and 41.2%, respectively. In conclusion, there is signifi cant eff ect of metformin and aspirin on SR cell line and only mild eff ect on NB4. These may be useful drugs in old diabetic patients with diff use large B cell lymphoma that may reduce the chemotherapy dose

Design and synthesis of new adamantyl derivatives as promising antiproliferative agents

A series of adamantyl carboxamide derivatives containing sulfonate or sulfonamide moiety were designed as multitargeted inhibitors of ectonucleotide pyrophosphatases/phosphodiesterases (NPPs) and carbonic anhydrases (CAs). The target compounds were investigated for their antiproliferative activity against NCI-60 cancer cell lines panel. Three main series composed of 3- and 4-aminophenol, 4-aminoaniline, and 5-hydroxyindole scaffolds were designed based on a lead compound (A). Compounds 1e (benzenesulfonyl) and 1i (4-fluorobenzenesulfonyl) of 4-aminophenol backbone exhibited the most promising antiproliferative activity. Both compounds exhibited a broad-spectrum and potent inhibition against all the nine tested cancer subtypes. Both compounds showed nanomolar IC50 values over several cancer cell lines that belong to leukemia and colon cancer such as K-562, RPMI-8226, SR, COLO 205, HCT-116, HCT-15, HT29, KM12, and SW-620 cell lines. Compounds 1e and 1i induced apoptosis in K-562 leukemia cells in a dose-dependent manner. Compound 1i showed the highest cytotoxic activity with IC50 value of 200 nM against HT29 cell line. In addition, compounds 1e and 1i were tested against normal breast cells (HME1) and normal skin fibroblast cells (F180) and the results revealed that the compounds are safe toward normal cells compared to cancers cells. Enzymatic assays against NPP1-3 and carbonic anhydrases II, IX, and XII were performed to investigate the possible molecular target(s) of compounds 1e and 1i. Furthermore, a molecular docking study was performed to predict the binding modes of compounds 1e and 1i in the active site of the most sensitive enzymes subtypes.

Combination of Tipifarnib and Sunitinib Overcomes Renal Cell Carcinoma Resistance to Tyrosine Kinase Inhibitors via Tumor-Derived Exosome and T Cell Modulation

Simple SummaryMetastatic renal cell carcinoma continues to have a poor prognosis. Chemotherapies and immuno-oncologic therapies have garnered increasing importance in cancer therapy, with improvements in patient care and survival. However, a large proportion of patients present with tumors resistant to these treatments. Exosomes are small extracellular vesicles secreted by all nucleated cells that have proven to be key actors in this resistance. Exosomes carry bioactive oncogenic cargos that reprogram target cells to promote tumor growth, migration, metastasis, immune evasion, and chemotherapy resistance. Tipifarnib, in combination with standard therapy, decreased tumor growth in the setting of chemotherapeutic resistance through an exosome-mediated mechanism. After using a qNANO IZON system to compare tumor-derived exosomes collected from untreated and tipifarnib-treated cells, all cancerous cell lines displayed a reduction of vesicle concentration. Tipifarnib also directly inhibited PD-L1 protein expression in chemo-sensitive cell lines and resistant cell lines.Background: Tyrosine kinase inhibitors (TKI) were initially demonstrated as an efficacious treatment for renal cell carcinoma (RCC). However, after a median treatment length of 14 months, a vast majority of patients develop resistance. This study analyzed a combination therapy of tipifarnib (Tipi) + sunitinib that targeted exosome-conferred drug resistance. Methods: 786-O, 786-O-SR (sunitinib resistant), A498, A498-SR, Caki-2, Caki-2-SR, and 293T cells were cultured. Exosomes were collected using differential ultracentrifugation. Cell proliferation, Jurkat T cell immune assay, and immunoblot analysis were used for downstream analysis. Results: SR exosomes treatment displayed a cytotoxic effect on immune cells. This cytotoxic effect was associated with increased expression of PD-L1 on SR exosomes when compared to sunitinib-sensitive (SS) exosomes. Additionally, Tipi treatment downregulated PD-L1 expression on exosomes derived from SR cell lines. Tipi’s ability to downregulate PD-L1 in exosomes has a significant application within patients. Exosomes collected from patients with RCC showed increased PD-L1 expression over subjects without RCC. Next, exosome concentrations were then compared after Tipi treatment, with all SS cell lines displaying an even greater reduction. On immunoblot assay, 293T cells showed a dose-dependent increase in Alix with no change in either nSMase or Rab27a. Conversely, all the SS and SR cell lines displayed a decrease in all three markers. After a cell proliferation employed a 48-h treatment on all SS and SR cell lines, the drug combination displayed synergistic ability to decrease tumor growth. Conclusions: Tipifarnib attenuates both the exosome endosomal sorting complex required for endosomal sorting complex required for transport (ESCRT)-dependent and ESCRT-independent pathways, thereby blocking exosome biogenesis and secretion as well as downregulating PD-L1 on SS and SR cells.

Synthesis, biological evaluation and molecular docking of new sulfonamide-based indolinone derivatives as multitargeted kinase inhibitors against leukemia

Series of novel sulfonamide-based 3-indolinones 3a-m and 4a-f were designed, synthesized and then their cytotoxic activity was evaluated against a panel of sixty cancer cell lines. This screening indicated that 4-(2-(5-fluoro-2-oxoindolin-3-ylidene)acetyl)phenyl benzenesulfonate (4f) possessed promising cytotoxicity against CCRF-CEM and SR leukemia cell lines with IC50 values 6.84 and 2.97 µM, respectively. Further investigation of the leukemic cytotoxicity of compound 4f was carried out by performing PDGFRα, VEGFR2, Aurora A/B and FLT3 enzyme assays and CCRF-CEM and SR cell cycle analysis. These investigations showed that compound 4f exhibited pronounced dual inhibition of both kinases PDGFRα and Aurora A with potency of 24.15 and 11.83 nM, respectively. The in vitro results were supported by molecular docking studies in order to explore its binding affinity and its key amino acids interactions. This work represents compound 4f as a promising anticancer agent against leukemia.

Synthesis and Anticancer Activity of 2-Cyano-N-(furan-2-ylmethyl)-2-(4-oxo-3-arylthiazolidin-2-ylidene)acetamide Derivatives

2-(4-Oxo-3-arylthiazolidin-2-ylidene)acetamide derivatives were prepared by the reaction of 2-cyano-N-furan-2-ylmethyl-3-sulfanyl-3-arylaminoacrylamides with chloroacetic acid, ethyl 3-aryl-2-bromopropanates, and acetylenedicarboxylic acid esters. 2-Cyano-N-furan-2-ylmethyl-2-(4-oxo-3-phenylthiazolidin-2-ylidene)acetamide reacted with pyridinecarbaldehydes and 5-arylfurfural to form the corresponding 5-heterylidene derivatives. The synthesized compounds were tested for anticancer activity. The most potent and selective cytotoxic effect was found in 2-(5-R-benzyl-4-oxo-3-arylthiazolidin-2-ylidene)-2-cyano-N-(furan-2-ylmethyl)acetamides against CCRF-CEM and SR leukemia cell lines.

Inhibition potency of disulphides and trisulphides on various tumor cell lines growth

Tumor is one of the leading diseases of today. Chemotherapy and radiation therapy healing chances are limited, so some alternative methods are resorted to. Many papers indicated that garlic and organosulphur compounds diallyldisulphide (DADS) and diallyltrisulphide, which are main components of garlic decrease the cancer risk and inhibit the cell proliferation. In this paper inhibition potency of disulphides (DADS and its synthetic analogues) and trisulphides with different alkyl and phenyl substituents on growth of various tumor (Non-Small cell Lung Cancer, Colon cancer, CNS Cancer, Melanoma, Ovarian Cancer, Renal Cancer, Prostate Cancer, Breast Cancer, Leukemia) cell lines was investigated. Concentration of each compound (DADS, diethyl disulphide, dipropyl disulphide, diphenyl disulphide, tetraethylthiuram disulphide (TETUDS), dimetil trisulphide, dipropyl trisulphide and metilpropyl trisulphide (MPTS) was 10 µmol/L. It was found that DADS has an inhibitory effect on the growth of several cancer cell lines, but synthetic analogues TETUDS and MPTS exhibit stronger effect on certain cells lines. MPTS inhibits the growth of even 12 cell lines for more than 10%, especially leukemia cell line SR and NCI-H522 cell line of Non-Small cell Lung Cancer (reduction of growth for 24% and 47%, resp.). Trisulphide analogues exhibit little higher inhibitory effects in comparison to disulphide ones.

Some pharmacological properties of 4-[3-(5-bromo-2-hydroxyphenyl)-5-phenyl-3,4-dihydropyrazol-2-yl]-5H-thiazol-2-one

A series of 3,5-diaryl pyrazolyl thiazolinones were designed and synthesized as potential biologically active compounds. The study of anticancer activity of 4-[3-(5-bromo-2-hydroxyphenyl)-5-phenyl-3,4-dihydropyrazol-2-yl]-5H-thiazol-2-one (1) revealed its high antiproliferative activity against a panel of cancer cells with the lowest growth inhibition concentration (GI50) towards leukemic cell line SR (0.0351 µМ) and ovarian cancer cell line OVCAR-3 (0.248 µМ). It was also found that pyrazolyl thiazolinone 1 inhibited growth of Trypanosoma brucei brucei by 98,8% at a concentration of 10 µg/mL. The in-depth cytotoxicity study of compound 1 on human hepatocellular carcinoma HepG2 cells and non-tumorigenic murine fibroblast Balb/c 3T3 in MTT, NRU, TPC and LDH assays showed that normal cells were less sensitive to compound 1 than the cancer cells; its action had led to a disintegration of the cell membrane, inhibition of mitochondrial and lysosomal activity, and proliferation of cancer cells. The highest selectivity were detected in the LDH assay.

New Paracyclophanylthiazoles with Anti-Leukemia Activity: Design, Synthesis, Molecular Docking, and Mechanistic Studies.

A new series of methyl 2-(2-(4′-[2.2]paracyclophanyl)-hydrazinylidene)-3-substituted-4-oxothiazolidin-5-ylidene)acetates 3a–f were synthesized from the reaction of paracyclophanyl-acylthiosemicarbazides 2a–f with dimethyl acetylenedicarboxylate. Based upon nuclear magnetic resonance (NMR), infrared (IR), and mass spectra (HRMS), the structure of the obtained products was elucidated. X-ray structure analysis was also used as unambiguous tool to elucidate the structure of the products. The target compounds 3a–f were screened against 60 cancer cell lines. They displayed anticancer activity against a leukemia subpanel, namely, RPMI-8226 and SR cell lines. The activity of compound 3a was found as the most cytotoxic potency against 60 cancer cell lines. Consequently, it was selected for further five doses analysis according to National Cancer Institute (NCI) protocol. The cytotoxic effect showed selectivity ratios ranging between 0.63 and 1.28 and between 0.58 and 5.89 at the GI50 and total growth inhibition (TGI) levels, respectively. Accordingly, compound 3a underwent further mechanistic study against the most sensitive leukemia RPMI-8226 and SR cell lines. It showed antiproliferation with IC50 = 1.61 ± 0.04 and 1.11 ± 0.03 µM against RPMI-8226 and SR cell lines, respectively. It also revealed a remarkable tubulin inhibitory activity, compared to colchicine with IC50 = 4.97 µM/mL. Caspase-3, BAX, and Bcl-2 assays for 3a using annexin V-FITC staining revealed significant pro-apoptotic activity. Furthermore, multidrug-resistant leukemia SR cells were used to show better resistance indices (1.285 ng/mL, 1.15-fold) than the reference. Docking studies with β-tubulin indicate that most of the tested compounds illustrated good binding at the colchicine binding site of the enzyme, especially for compound 3a, which made several interactions better than that of the reference colchicine.

Development of a Brigatinib degrader (SIAIS117) as a potential treatment for ALK positive cancer resistance

EML4-ALK and NPM-ALK fusion proteins possess constitutively activated ALK (anaplastic lymphoma kinase) activity, which in turn leads to the development of non-small cell lung cancer and anaplastic large-cell lymphomas (ALCLs). FDA-approved ALK inhibitor drugs cause significant cancer regression. However, drug resistance eventually occurs and it becomes a big obstacle in clinic. Novel proteolysis targeting chimera (PROTAC) technology platform provides a potential therapeutic strategy for drug resistance. Herein, we designed and synthesized a series of ALK PROTACs based on Brigatinib and VHL-1 conjunction, and screened SIAIS117 as the best degrader which not only blocked the growth of SR and H2228 cancer cell lines, but also degraded ALK protein. In addition, SIAIS117 also showed much better growth inhibition effect than Brigatinib on 293T cell line that exogenously expressed G1202R-resistant ALK proteins. Furthermore, it also degraded G1202R mutant ALK protein in vitro. At last, it has the potentially anti-proliferation ability of small cell lung cancer. Thus, we have successfully generated the degrader SIAIS117 that can potentially overcome resistance in cancer targeted therapy.

1,2,3-Triazole-Chalcone hybrids: Synthesis, in vitro cytotoxic activity and mechanistic investigation of apoptosis induction in multiple myeloma RPMI-8226

A new series of 1,2,3-triazole-chalcone hybrids has been synthesized and screened in vitro against a panel of 60 human cancer cell lines according to NCI (USA) protocol. Compound 4d having 3, 4-dimethoxyphenyl chalcone moiety, the most potent derivative, inhibited the growth of RPMI-8226 and SR leukemia cell lines by 99.73% and 94.95% at 10 μM, respectively. Also, it inhibited the growth of M14 melanoma, K-562 leukemia, and MCF7 breast cancer cell lines by more than 80% at the same test concentration. 4d showed IC50 values less than 1 μM on six types of tumor cells and high selectivity index reached to 104 fold on MCF7. Compound 4d showed superior activity than methotrexate and gefitinib against the most sensitive leukemia cell lines in addition to higher or comparable activity against the rest sensitive cell lines. Flow cytometry analysis in RPMI-8226 cells revealed that compound 4d caused cell cycle arrest at G2/M phase and induced apoptosis in a dose dependant manner. Mechanistic evaluation referred this apoptosis induction to triggering mitochondrial apoptotic pathway through inducing ROS accumulation, increasing Bax/Bcl-2 ratio and activation of caspases 3, 7 and 9.

BIOCOMPATIBILITY STUDY OF α-Fe2O3NANOPARTICLES PREPARED BY HYDROTHERMAL METHOD

Nanoparticles of alpha ferric oxide ([Formula: see text]-Fe2O3) were prepared by the hydrothermal method. Structural properties of [Formula: see text]-Fe2O3were determined by XRD, SEM and AFM measurements. The particles had a good matching with standard pattern. Average particle size was about 90[Formula: see text]nm and the distribution extended from about 20[Formula: see text]nm to 120[Formula: see text]nm. Biocompatibility study of ferric oxide nanoparticles against bacteria, parasites, tumor cell line and normal cells was determined. No antibacterial activity was observed for the concentration, of ferric oxide nanoparticles in distilled water, up to 1.5[Formula: see text]mg/ml vs. E. coli and S. aureus. Moreover, MTT assay was used to determine the cytotoxicity against parasites and cells. Intermediate cytotoxicity (53.30%) of 1.5[Formula: see text]mg/ml of prepared nanoparticles was noted against L. tropica, while weak cytotoxicity of 5.20% was observed against L. donovani at the same concentration of ferric oxide nanoparticles. On the other hand, the prepared nanoparticles revealed low cytotoxicity (47.28%) against SR tumor cell line, while no cytotoxicity was shown against lymphocytes, as a model of normal cells.

Structural tuning of acridones for developing anticancer agents targeting dihydrofolate reductase.

Targeting dihydrofolate reductase, here, we report the tumor growth inhibitory activity of substituted acridones. The screening of the molecules over 60 cell line panel of human cancer cells identified (S)-oxiran-2-ylmethyl 9-oxo-9,10-dihydroacridine-4-carboxylate (19) with average GI50 0.3 μM. The specificity of the compound to CCRF-CEM, MOLT-4 and SR cell lines of leukemia and SW-620, SF268, LOXIMVI, ACHN and MCF7 cancerous cells exhibiting GI50 in the nM range was observed. C6 Glioma cells treated with compound 19 showed differentiated cell morphology and cell cycle arrest in G2/M phase. The interactions of the compound with dihydrofolate reductase were ascertained with the help of enzyme immunoassays, molecular docking and molecular dynamic studies.

Novel nalidixic acid derivatives targeting topoisomerase II enzyme; Design, synthesis, anticancer activity and effect on cell cycle profile

AimDesign and synthesis of novel nalidixic acid derivatives of potent anticancer and topoisomerase II inhibitory activities were our major aim. Materials & methodsAll the newly synthesized nalidixic acid derivatives were submitted to the National Cancer Institute (NCI), Bethesda, USA and were accepted for single dose screening. Further investigation via IC50 determination of the most potent compound 6a against K-562 and SR leukemia cell lines. Finally, the topoisomerase II inhibitory activity, the cell cycle analysis and molecular docking of 6a were performed in order to identify the possible mechanism of the anticancer activity. ResultsCompound 6a showed interesting selectivity against leukemia especially K-562 and SR subpanels with IC50 35.29 µM and 13.85 µM respectively. Moreover, compound 6a revealed potent topoisomerase IIα and topoisomerase IIβ inhibitory activity compared with known topoisomerase inhibitors such as doxorubicin and topotecan with IC50 1.30 µM and 0.017 µM respectively. Cell cycle analysis indicated that compound 6a induced cell cycle arrest at G2-M phase leading to inhibition of cell proliferation and apoptosis. Molecular modeling demonstrated that the potent topoisomerase inhibitory activity of 6a was due to the interaction with the topoisomerase II enzyme through coordinate bonding with the magnesium ion Mg2+, hydrogen bonding with Asp 545 and arene cation interaction with His 759.

Design and synthesis of novel 5-(4-chlorophenyl)furan derivatives with inhibitory activity on tubulin polymerization.

Discovery of novel series of colchicine binding site inhibitors (CBSIs). Isoxazoline 3a-d, pyrazoline 4a-b, 7a-f and 8a-f, cyclohexenone 9a-b and 10a-b or pyridine derivatives 11a-b were synthesized and evaluated for their inhibition of tubulin polymerization and cytotoxicity. Most of the compounds displayed potent to moderate antitumor activity against leukemia SR cell line.7c, 7e and 11a were more potent than colchicine with IC50 of 0.09, 0.05 and 0.06μM, and percentage inhibition in tubulin polymerization of 95.2, 96.0 and 96.3%, respectively. Compounds 7c and 11a showed cell-cycle arrest at G2/M phase and induced apoptosis and were able to bind the colchicine binding site of tubulin with comparable affinity to colchicine. Docking study showed that these compounds may interact with tubulin exploiting a binding cavity not commonly reported in the binding of CBSI. Compounds 7c and 11a may be considered as promising CBSI based on their excellent activity and favorable drug likeness profile.

Naphthalene diimide-polyamine hybrids as antiproliferative agents: Focus on the architecture of the polyamine chains

Naphthalene diimides (NDIs) have been widely used as scaffold to design DNA-directed agents able to target peculiar DNA secondary arrangements endowed with relevant biochemical roles. Recently, we have reported disubstituted linear- and macrocyclic-NDIs that bind telomeric and non-telomeric G-quadruplex with high degree of affinity and selectivity. Herein, the synthesis, biological evaluation and molecular modelling studies of a series of asymmetrically substituted NDIs are reported. Among these, compound 9 emerges as the most interesting of the series being able to bind telomeric G-quadruplex (ΔTm = 29 °C at 2.5 μM), to inhibit the activity of DNA processing enzymes, such as topoisomerase II and TAQ-polymerase, and to exert antiproliferative effects in the NCI panel of cancer cell lines with GI50 values in the micro-to nanomolar concentration range (i.e. SR cell line, GI50 = 76 nM). Molecular mechanisms of cell death have been investigated and molecular modelling studies have been performed in order to shed light on the antiproliferative and DNA-recognition processes.

Quantum modelling of the Structure-Activity and toxicity relationship studies of some potent compounds on SR leukemia cell line

Abstract In this study, a data set of one hundred (100) compounds from NCI database were optimized at the density functional theory (DFT) level using Becke's three-parameter Lee–Yang–Parr hybrid functional (B3LYP) in combination with the 6–31G* basis set. The optimized structures were employed in the generation of quantum chemical and molecular descriptors. These were then divided into training and test sets by Kennard Stone algorithm. The QSAR models were generated using the Genetic Function Approximation (GFA). The developed models were then subjected to internal and external validation and Y-randomization tests in order to establish their predictability and reliability. Descriptors such as number of methanal group (nMethanal), Secondary butyl, Sum of atom-type E-State:-F (S_Sf), Excessive molar refraction (MLFER_E) and 3D topological distance based autocorrelation - lag 3/weighted by first ionization potential (TDB3i) were found to be principally responsible for the activity nature of the compounds on SR cell lines, while Geary autocorrelation - lag 7/weighted by first ionization potential (GATS7i), Spectral mean absolute deviation from Barysz matrix/weighted by van der Waals volumes (SpMAD_Dzv) and number of high lowest atom weighted BCUTS (BCUTW-1i) chemical descriptors mean effects in the LC 50 model indicates their high influence on the toxicity of these compounds on SR cell line.

Synthesis and antitumor evaluation of trimethoxyanilides based on 4(3H)-quinazolinone scaffolds

A novel series of 2-[(3-substituted-4(3H)-quinazolin-2-yl)thio]-N-(3,4,5-trimethoxyphenyl)acetamide (15–21) and 3-[(3-substituted-4(3H)-quinazolin-2-yl)thio])-N-(3,4,5-trimethoxyphenyl)propanamide (23–29) were designed, prepared and estimated for their anticancer activity in a solo dose 10 μM of the test compounds in the NCI 57 cell lines panel assay. Compounds 20, 23, 26, 27 and 28 revealed extensive-spectrum antitumor efficiency to numerous cell lines that belong to various tumor subpanels, while compounds 15, 16 and 19 possessed perceptive activity toward A498 and UO-31 renal cancer cell lines, and compound 17 showed selective effectiveness against NSC lung cancer NCI-H522 cell line. Additionally, compound 18 showed advanced activity against SR leukemia cell line, NSC lung cancer HOP-92 and renal cancer UO-31 cell lines.