Biological Activity, Lipophilicity and Cytotoxicity of Novel 3-Acetyl-2,5-disubstituted-1,3,4-oxadiazolines

Antibiotic resistance is now a global problem, and the lack of effective antimicrobial agents for the treatment of diseases caused by resistant microbes is increasing. The 3-acetyl-2,5-disubstituted-1,3,4-oxadiazolines presented in this article may provide a good starting point for the development of potential new effective antimicrobial agents useful in the treatment of bacterial and fungal infections. Particular attention is drawn to the 1,3,4-oxadiazole derivative marked with the number 29 with 5-nitrofuran-2-yl substituent in its chemical structure. This substance showed a strong bactericidal effect, especially against Staphylococcus spp., and no cytotoxicity to the L929 normal cell line.

Two New Isoprenoid Flavonoids from Sophora flavescens with Antioxidant and Cytotoxic Activities

Sophora flavescens is a regularly used traditional Chinese medicine. In an attempt to discover adequate active agents, the isoprenoid flavonoids from S. flavescens were further investigated. In this work, two new compounds (1–2, kurarinol A-B) together with 26 known ones (3–28) were isolated and elucidated on the basis of extensive NMR, UV and MS analyses. Furthermore, the antioxidant activity of all constituents was assessed through ABTS, PTIO and DPPH methodologies and also were evaluated for cytotoxic activity by three tumor cell lines (HepG2, A549 and MCF7) and one human normal cell line (LO2 cells). As a result, a multitude of components revealed significant inhibitory activity. In particular, compound 1–2 (kurarinol A-B), two new flavanonols derivatives, exhibited the most potent ABTS inhibitory activity with IC50 of 1.21 µg/mL and 1.81 µg/mL, respectively. Meanwhile, the new compound 1 demonstrated remarkable cytotoxicity against three cancer cells lines with IC50 values ranging from 7.50–10.55 μM but showed little effect on the normal cell. The two new isoprenoid flavonoids could be promising antioxidant and anti-tumor nature agents.

Synthesis of Functional Building Blocks for Type III-B Rotaxane Dendrimer

Second-generation type III-B rotaxane dendrons, equipped with succinimide and acetylene functional groups, were synthesized successfully and characterized by NMR spectroscopy and mass spectrometry. A cell viability study of a dendron with a normal cell line of L929 fibroblast cells revealed no obvious cytotoxicity at a range of 5 to 100 μM. The nontoxic properties of the sophisticated rotaxane dendron building blocks provided a choice of bio-compatible macromolecular machines that could be potentially developed into polymeric materials.

Design, Synthesis and Bioactivity Evaluation of Novel Chalcone Derivatives Possessing Tryptophan Moiety with Dual Activities of Anti-cancer and Partially Restoring the Proliferation of Normal Kidney Cells Pre-treated with Cisplatin

Background: Chalcone is a broad-spectrum natural product with anti-cancer and anti-inflammatory activities. However, low potency, low selectivity, and serious side effects limit its druggability. L-Tryptophan is an essential precursor molecule of an anti-cancer active substance. Also, the indole moiety inhibits the proliferation of tumor cells by binding to colchicine sites. A decrease in kidney cell activity caused by kidney inflammation is the primary side effect of cancer therapy. Objective: The purpose of this work was to design, synthesize, and perform bioactivity evaluation of novel chalcone derivatives possessing tryptophan moiety with dual activities of anti-cancer and partially restoring the proliferation of normal kidney cells pre-treated with cisplatin. Methods: A series of novel chalcone derivatives possessing tryptophan moiety (5a-5g, 6a-6o) were designed, synthesized, and evaluated for anti-cancer activity against four cancer cell lines (gastric (HGC-27), colon (HCT-116), prostate (PC-3), and lung (A549)), and a human normal cell line (gastric mucosal epithelial (GES-1)). The activity of restoring the proliferation of normal kidney cells pre-treated with cisplatin was evaluated by MTT assay. Cell cycle, apoptosis, and apoptosis proteins (Bax and Bcl-2) were used to evaluate the anti-cancer mechanism of the most potent compound. Moreover, a docking study was performed to explain the high anti-cancer activity of 6n. The expressions of TNF-α, IL-6, and MCP-1 were detected by ELISA. Results: Most of the compounds exhibited high anti-cancer activity against the HGC-27 cell line and exhibited low toxicity against the normal cell line. Based on three rounds of a structure optimization, 6n was discovered as the most potent compound against HGC-27 cells with an IC50 value of 2.02 μM and an SI value of 28.47. Further studies demonstrated that 6n could induce cell cycle arrest at the G2/M phase and the apoptosis of the HGC-27 cell line by reducing the expression of Bcl-2 and improving the expression level of Bax. Molecular docking result displayed 6n bound to the colchicine site. At the same time, 6n also exhibited moderate activity of restoring the proliferation of normal kidney cells pre-treated with cisplatin by reducing the expression of inflammatory substances. Conclusion: Our findings collectively suggested that 6n should be further studied as a potential anti-cancer agent that could partially restore the proliferation of normal kidney cells pre-treated with cisplatin in gastric cancer patients by an anti-inflammatory pathway.

In-vitro Testing of Antioxidant, Anti-Parasite Activities, Cytotoxicity, and Chemical Evaluation of Abutilon Pannosum and Cassia Occidentalis Ethanolic Extracts

Aims: The aim of this study to detect Anti-giardia, antioxidant activities, cytotoxicity and evaluated the chemical constituent of ethanolic extracts of Abutilon pannosum and Cassia occidentalis. Study Design: Various standard methods were used to detect of bioactivity for ethanolic extracts of plants used in this study. Place and Duration of Study: This study was conducted in the laboratories of microbiology and parasitology and chemistry, the International University of Africa, Khartoum, Sudan, during May 2019. Methodology: The ethanolic extract of Abutilon pannosum and Cassia occidentalis was used as an anti-giardia and anti-oxidant in-vitro, and toxicity tests were performed using brine shrimp and MTT assay. Also, the compounds of the plants used were detected by the GCMS apparatus. Results: The ethanolic extracts of Abutilon pannosum showed high Anti-giardia activity (79%) in concentration (500 ppm) after 72 hours, whereas the activity of Cassia occidentalis extract showed (61%). The highest antioxidant activity of ethanolic extract of Cassia occidentalis was (68.7%), while it was weak in Abutilon pannosum ethanolic extract (45%) by using 2,2-diphenyl-1-picrylhydrazyl (DPPH) assay. The results of cytotoxicity revealed that the ethanolic extracts are highly toxic to brine shrimp, but are not toxic to normal cell line (MTT). Chromatographic analysis using gas chromatography-mass spectroscopy (GCMS) showed good separation of compounds. GCMS detected 22 and14 important compounds in Abutilon pannosum and Cassia occidentalis extracts respectively. The common compound in both plant extracts is n-Hexadecanoic acid. This acid was reported as an antioxidant. Conclusion: This study revealed that the biological activities of Abutilon pannosum extracts showed high activities of Anti-giardia and antioxidants. Non-cytotoxic in the normal cell line was shown. Cassia occidentalis showed high activity of Anti-giardia and weak activity antioxidant.

The Antiproliferative, Antioxidant Activities and Toxicity of Mixed-Ligand Amine-Containing Copper (II) Coordination Compounds with 2-(2-Hydroxybenzylidene)-N-(Prop-2-En-1-Yl) Hydrazinecarbothioamide

Five compounds 2-(2-Hydroxybenzylidene)-N-(prop-2-en1-yl)hydrazinecarbothioamide (H2L), bis[μ2-2-({2-[(prop-2-en-1-yl) carbamothioyl] hydrazinylidene}methyl) phenolatoS,N,O:O] diaquadicopper (II) nitrate (1), bis [μ2-2-({2-[(prop-2-en-1-yl) carbamothioyl] hydrazinylidene}methyl)phenolato-S,N,O:O]d iimidazoldicopper(II) nitrate (2), bis[μ2-2-({2-[(prop-2en-1-yl)carbamothioyl]-hydrazinylidene}methyl)phenolato-S,N,O:O]bis-(3,5-dibromopyridine)dicopper( II) nitrate hexahydrate (3), bis[μ2-2-({2-[(prop-2-en-1-yl)carbamothioyl]-hydrazinylidene}methyl) phenolato-S,N,O:O]bis(4-methylpyridine)dicopper(II) nitrate hexahydrate (4) were synthesized. The antiproliferative properties of these compounds towards cancer cell lines HeLa, RD and normal cell line MDCK have been investigated. The tested compounds demonstrated high antioxidant and antiproliferative, selective activities towards cancer cells. Direct toxic evaluation of compounds was performed by Daphnia magna bioassay.

EMBRYOTOXICITY AND TERATOGENIC EFFECTS OF PARMOTREMA TINCTORUM (NYL) HALE ON ZEBRAFISH (DANIO RERIO) AND CYTOTOXIC ACTIVITY OF LICHEN EXTRACT ON HEK293T CELL LINE

Parmotrema tinctorum (Nyl) Hale an edible lichen, used as a spice and flavouring agent for meat and vegetable preparations by ethnic groups in India and Nepal. In Zebrafish embryos and larva, the therapeutic applications of P.tinctorum widely reported. However the teratogenic effects not reported. This study was aimed to examine the toxicity of P.tinctorum on the promising model for toxicity research, the Zebrafish, because their genetic structure is more similar to human beings. Additionally, we have demonstrated a toxic effect of P.tinctorum extract on the human normal cell line (HEK293T) by MTT assay. The methanol extract of P.tinctorum was extracted by Soxhlet and for embryotoxicity and teratogenicity activities, we use different concentrations (50µg/ml – 200µg/ml) of lichen extracts on twelve selected fertilized Zebrafish embryos. The extract did not exhibit any effect on Zebrafish Survival rate, hatching rate, heartbeat and teratogenicity which was similar to control groups. To conclude that, methanol extract of P.tinctorum is found to have a nontoxic property to zebrafish embryo and human normal cell line (HEK293T) and suggests that this might be safe for consumption

Exploring anticancer activity of wild and polyploid mutant of Artemisia cina

Kasmiyati S, Kristiani EBE, Herawati MM, Rondonuwu FS. 2021. Exploring anticancer activity of wild and polyploid mutant of Artemisia cina. Biodiversitas 22: 1227-1234. The research aims were to explore the anticancer compounds in wild type (W) and polyploid mutant (P) of Artemisia cina Berg ex Poljakov using NIR and compare their cytotoxicity and selectivity on WiDR colon cancer and HTB183 lung cancer cell lines and Vero normal cell line. The W was obtained from B2P2TOOT Tawangmangu, Indonesia while P was by inducing A. cina shoot culture with 100 mg/l colchicine for 48 hours. They were extracted with hexane using the soxhletation method for 6 hours. The anticancer compounds were detected using NIR. The cytotoxic activity was determined using MTT assay, with Doxorubicin (D) as a control. The calculation of IC50 value used SPSS16 with a Probit analysis. The P contained the determined four compounds while the W contained no rutin. The IC50 values of W, P, and D were 295.5, 84.1, and 0.5 µg/mL on WiDr, 322.4, 128.6, and 39.9 µg/mL on HTB 183, whereas on Vero were 104, 315.6, and 295.5 µg/mL respectively. The selectivity indexes of W, P, and D were 34, 4, and 91 on WiDr, while HTB 183 was 31, 3, and 7, respectively. The P contained artemisinin, quercetin, kaemferol, and rutin, while the W contained no rutin. The cytotoxicity of both plants was less than doxorubicin. Both plants were selective on WiDR and HTB 183.