Cytological aspects of haemoglobin and chlorocruorin synthesis in polychaete annelids

Summary The ultrastructure of the haematopoietic cells in the polychaetes Neoamphitrite figulus Dalyell, Lanice conchilega (Pallas), Arenicola marina (L.), Myxicola infundibulum Renier, Megalomma vesiculusom (Montagu), Sabella penicillus L., are compared: all show similarities in having well developed Golgi, granular endoplasmic reticulum and haemoglobin or chlorocruorin in vesicles, and numerous mitochondria. The porphyrin byproducts of synthesis are combined with iron as haematins within electrondense granules built up from multi-lamellar organelles. The structure of the basal lamina which alone separates the cells from the lumen of the vessels is described and evidence is presented for the method of release of the haem into the plasma by reverse pinocytosis. The cycle of synthesis within the cell is discussed and the process of haem synthesis in annelids is reviewed. The structure of the haemoglobin-containing coelomocytes of Neoamphitrite figulus is briefly described.This work was made possible by an award from the Science Research Council. We would also like to thank the Director and Staff of the Plymouth Laboratory, where some of the work was done, for their hospitality and facilities.     

Synthesis and antitumor activity of three novel ginsenoside M1 derivatives with 3′-ester modifications

Ginsenoside M1 (M1) was considered to be the main antitumor component of ginsenoside metabolites in the body. In order to enhance its potency on antitumor effect, three novel M1 3′–ester derivatives (1c, 2c, 3c) were synthesized and evaluated. The yield of these derivatives was between 41% and 69%. Compared with M1, 2c and 3c can improve the efficacy of the inhibition on breast cancer MCF–7 and MDA–MB–231 cells, especially for MCF–7 (fold: 0.7–4.2, p < 0.0001). Further study suggested that 2c and 3c may cause cell autophagy and promote apoptosis in MCF–7 cells. The results indicated the 3′–ester modified M1 derivatives 2c and 3c possess higher abilities of inhibition growth towards triple–positive breast cancer and provided a new source for synthesis of potential anti-breast cancer drugs.     

Synthesis,antitumor testing and molecular modeling study of some new 6-substituted amido,azo or thioureido-quinazolin-4(3H)-ones

A new series of 6-substituted amido, azo or thioureido-quinazolin-4(3H)-one was synthesized and tested for their in-vitro antitumor activity. Compounds 21, 53 and 60 showed broad spectrum antitumor activity with average IC₅₀ values of 6.7, 7.6 and 9.1 μM, respectively compared with methotrexate (1, IC₅₀ 19.26 μM). As an attempt to reveal the mechanism of the antitumor potency, cell cycle analysis and DHFR inhibition were performed. Compounds 59 and 61 induced their cytotoxicity in Hela (IC₅₀ 10.6 μM) and HCT-116 (IC₅₀ 15.5 μM) cell lines, respectively through Pre-G1 apoptosis, inhibiting cell growth at G2-M phase. Compounds 29, 33, 59 and 61 showed DHFR inhibitory potency at IC₅₀ 0.2, 0.2, 0.3 and 0.3 μM, respectively. The active DHFR inhibitors showed high affinity binding toward the amino acid residues Thr56, Ser59 and Ser118. The active compounds obeyed Lipinski’s rule of five and could be used as template model for further optimization.     

The novel economical synthesis and antimicrobial activity of a trithiocarbonate derivative

The compound diethyl 2,2′-(thiocarbonyl-bis(sulfanediyl))-diacetate 4 belongs to the trithiocarbonate class containing a trithiocarbonate function group flanked by ethyl acetate. In this procedure, a novel economic synthesis route to obtain compound 4 is described. This compound proved to possess broad-spectrum antimicrobial activity both in vitro and in vivo, and could be used as a lead compound. It is worth mentioning that this compound has been patented [No. US 9,988,348 B1; date of patent: June 5, 2018].     

Synthesis of benzothiazole derivatives as a potent α-glucosidase inhibitor

Diabetes is one of the pre-dominant metabolic disorders all over the world. It is the prime reason of mortality and morbidity due to hyperglycemia which is link with numerus obstacles. Delaying absorption and digestion of carbohydrate has great therapeutic impact for governing postprandial hyperglycemia. Consequently, alpha glucosidase is one of the potential therapeutic approaches that reduce absorption of glucose and delay carbohydrate digestion hence maintaining blood glucose level. In this regard we have synthesized benzothiazole based oxadiazole in search of potent anti-diabetic agent as α-glucosidase Inhibitors. Benzothiazole based oxadiazole derivatives 1–23 have been synthesized, characterized by ¹HNMR, ¹³CNMR, and MS and evaluated for α-glucosidase Inhibition. All analogs exhibited a varying degree of α-glucosidase inhibitory activity with IC₅₀ values ranging in between 0.5 ± 0.01–30.90 ± 0.70 μM when compared with the standard acarbose (IC₅₀ = 866.30 ± 3.20 μM). Structure activity relationship has been established for all compounds. Molecular docking studies were performed to predict the binding interaction of the compounds with the active site of enzyme.     

Synthesis,characterization, antioxidant power and acute toxicity of some new azo-benzamide and azo-imidazolone derivatives with in vivo and in vitro antimicrobial evaluation

In this research paper, a stepwise chemical reaction was conducted to synthesize and develop of a new potent azo-oxazolone, which was used as prototypical molecule for production of two series of azo-benzimide (5a–j) and azo-imidazolone (6a–j). FT-IR, ¹H NMR, ¹³C NMR and CHN analysis were used for the structural elucidation. The high biological efficiency of newly obtained compounds was confirmed by in vitro antioxidant efficacy and in vitro antimicrobial activity against gram-positive and gram-negative bacteria via disc diffusion and tube dilution techniques. In addition, in vivo anti-microbial activity of some of the synthesized compounds was determined by using burnt rats which infected by Staphylococcus aureus. Tested compounds have shown high anti-microbial activity and wound healing in comparison to ucederm as a control. In vivo acute toxicity was carried out by up and down method for the compounds 4, 5d and 6d. The limited test dose was 2000 mg/kg, while the maximum tolerated dose was 5000 mg/kg which has administered no lethality recorded.     

Design and synthesis of new benzoxazole/benzothiazole-phthalimide hybrids as antitumor-apoptotic agents

Herein, we synthesized a series of twelve benzoxazole and benzothiazole derivatives incorporated with phthalimide core as anticancer agents. The most active compounds were 5a and 5g against HepG2 and MCF7 cell lines with IC₅₀ = 0.011 and 0.006 μM, respectively.They evaluated against EGFR and HER2 enzymes. From cell cycle analysis, it was observed that test compounds exerted pre G1 apoptosis and cell cycle arrest at G2/M phase. The achieved results suggested that apoptosis was due to activation of caspase-7 and caspase-9. EGFR was chosen as a biological target for carrying molecular modeling study for the newly synthesized compounds.     

多不饱和脂肪酸合成途径研究进展

多不饱和脂肪酸在大多数生物体膜生物学和信号传递过程中起着至关重要的作用。最近研究发现,一些深海生物合成多不饱和脂肪酸并非由饱和脂肪酸的延长及脱饱和反应,而是由聚酮合酶途径(polyketide synthase,PKS)直接合成。介绍多不饱和脂肪酸的生物合成并总结近年来聚酮合酶这一新途径及其分子机制的研究进展。     

Synthesis and biological evaluation of novel N-substituted 1H-dibenzo[a,c]carbazole derivatives of dehydroabietic acid as potential antimicrobial agents

A series of new N-substituted 1H-dibenzo[a,c]carbazole derivatives were synthesized from dehydroabietic acid, and their structures were characterized by IR, ¹H NMR and HRMS spectral data. All compounds were evaluated for their antibacterial and antifungal activities against four bacteria (Bacillus subtilis, Staphylococcus aureus, Escherichia coli and Pseudomonas fluorescens) and three fungi (Candida albicans, Candida tropicalis and Aspergillus niger) by serial dilution technique. Some of the synthesized compounds displayed pronounced antimicrobial activity against tested strains with low MIC values ranging from 0.9 to 15.6 μg/ml. Among them, compounds 6j and 6r exhibited potent inhibitory activity comparable to reference drugs amikacin and ketoconazole.     

Synthesis and biological evaluation of novel pazopanib derivatives as antitumor agents

A series of novel pazopanib derivatives, 7a–m, were designed and synthesized by modification of terminal benzene and indazole rings in pazopanib. The structures of all the synthesized compounds were confirmed by ¹H NMR and MS. Their inhibitory activity against VEGFR-2, PDGFR-α and c-kit tyrosine kinases were evaluated. All the compounds exhibited definite kinase inhibition, in which compound 7l was most potent with IC₅₀ values of 12 nM against VEGFR-2. Furthermore, compounds 7c, 7d and 7m demonstrated comparable inhibitory activity against three tyrosine kinases to pazopanib, and compound 7f showed superior inhibitory effects than that of pazopanib.