Syntheses, Molecular Docking and Biological Evaluation of 2-(2- hydrazinyl)thiazoles as Potential Antioxidant, Anti-Inflammatory and Significant Anticancer Agents.

BACKGROUND: Recently, researchers have worked on the development of new methods for the synthesis of bioactive heterocycles using polyethylene glycol as a green solvent. In this context, we report the synthesized 2-(2-hydrazinyl) thiazoles for their in vitro antioxidant, in vitro anti-inflammatory and in vitro anti-cancer activities. OBJECTIVE: The objective of the study was to develop novel antioxidant, anti-inflammatory and anti-cancer drugs. METHODS: At the outset, the condensation of substituted acetophenones 1, thiosemicarbazide 2, and α-haloketones 3 was carried out using PEG-400 (20 mL) in the presence of 5 mol% glacial acetic acid to afford thiosemicarbazones intermediate. Furthermore, these thiosemicarbazones were reacted with α-haloketones 3 to obtain appropriate 2-(2-hydrazinyl) thiazoles. The synthesized compounds were in vitro tested for their antioxidant, anti-inflammatory, and anti-cancer activity. RESULTS: In vitro evaluation report showed that nearly all molecules possessed potential antioxidant activity against 2,2-Diphenyl-1-picrylhydrazyl (DPPH), nitric oxide (NO), superoxide radical (SOR) and hydrogen peroxide (H2O2) radical scavenging activity. Most 2-(2-hydrazinyl) thiazoles derivatives have shown potential anti-inflammatory activity as compared to diclofenac sodium as a reference standard. 2-(2-Hydrazinyl) thiazoles derivatives showed significant anticancer activity for human leukemia cell line K-562 compared to adriamycin as a reference standard. CONCLUSION: All tested compounds showed potential 2,2-Diphenyl-1-picrylhydrazyl (DPPH) and nitric oxide (NO) radical scavenging activity. Among the tested series, 4b, 4d and 4e exhibited good hydrogen peroxide and 4b, 4e, 4f and 4g showed excellent superoxide radical scavenging activity. In addition, the 4b, 4e and 4g compounds revealed potent in vitro anti-inflammatory activity against standard diclofenac sodium drug. 2-(2-Hydrazinyl) thiazole derivatives, such as 4c and 4d, showed significant anticancer activity against human leukemia cell line K-562. Thus, these molecules provide an interesting template for the design and development of new antioxidant, anti-inflammatory, and anti-cancer agents.

A Novel Method for the Syntheses of Imidazo-Thiadiazoles as Potential Antioxidants and Anti-Inflammatory Agents.

BACKGROUND: A literature survey revealed that many imidazo-thiadiazole molecules were used as key intermediates for the development of novel drugs. The synthesized imidazo-thiadiazole derivatives were tested for their in vitro antioxidant and anti-inflammatory properties. The purpose of this research paper is to provide readers with information regarding diseases caused by free radicals. OBJECTIVE: The objective of this study is to develop novel antioxidant and anti-inflammatory drugs. METHODS: Imidazo-thiadiazole derivatives 5a-f were synthesized through cyclo-condensation reactions in two steps. First, the synthesis of 2-amino-thiadiazole derivatives from substituted aromatic carboxylic acids and thiosemicarbazide by using POCl3 as a solvent as well as a catalyst was performed. In the next step, imidazo-thiadiazoles were prepared from 2-amino-thiadiazole derivatives with appropriate α-haloketones in the presence of polyethylene glycol-300 (PEG-300) as a green solvent. These imidazo- thiadiazole derivatives were prepared by using a novel method. The synthesized compounds were in vitro tested for their antioxidant and anti-inflammatory activities. RESULTS: In vitro evaluation report showed that nearly all molecules possess potential antioxidant activity against 2,2-diphenyl-1-picrylhydrazyl (DPPH), nitric oxide (NO), superoxide radical (SOR), and hydrogen peroxide (H2O2) radical scavenging activity. Most of the imidazo-thiadiazole derivatives have shown significant anti-inflammatory activity as compared to diclofenac sodium as a reference standard. CONCLUSION: In the search for novel therapies to treat inflammation and oxidation, we have made efforts to develop anti-inflammatory and antioxidant agents with a preeminent activity. Imidazo-thiadiazoles 5a, 5e as well as 5f showed potential anti-inflammatory activity. All tested imidazo-thiadiazole deriv-atives (5a-f) showed potential antioxidant activity against one more radical scavenging species as com-pared to ascorbic acid as the reference standard. Thus, imidazo-thiadiazole derivatives constitute an interesting template for the design and development of new antioxidant as well as anti-inflammatory agents.

Metal-free oxidative coupling of arylmethylamines with indoles: a simple, environmentally benign approach for the synthesis of 3,3'-bis(indolyl)methanes.

The efficient metal-free oxidative coupling of arylmethylamines with indoles has been developed using molecular oxygen as a green oxidant. The present reaction provides a novel route towards the synthesis of 3,3'-bis(indolyl)methanes in excellent yields of up to 95% via C-C and C-N bond formation. This attractive and environmentally friendly one-pot protocol is a simple procedure that features inexpensive acetic acid as the catalyst and molecular oxygen as the sole oxidant, and it supports a wide substrate scope with the good tolerance of functional groups.

Synthesis of Asymmetric 1-Thiocarbamoyl Pyrazoles as Potent Anti- Colon Cancer, Antioxidant and Anti-Inflammatory Agent.

BACKGROUND: Cancer is one of the leading diseases responsible for deaths in the society. According to the American cancer society, there will be 95,270 new cases of colon cancer in the U.S. in 2016. When a normal cell turns cancerous they develop into tumours, which produce various pro-inflammatory and inflammatory cytokines and chemokines that attract leukocytes to the site of growth. The main aim of this paper is to introduce readers about the increased number of cancer patient, effects of cancer and need of research on same. METHODS: The target molecules were prepared by reacting pyrazolealdehyde with appropriate aromatic ketone by using polyethylene glycol (PEG-300) as green solvent and catalyst to yield chalcone. Furthermore, the reaction of chalcones with thiosemicabazide yields asymmetric 1-thiocarbamoyl pyrazoles. All the newly synthesized compounds were in vitro screened for their anticancer activities against Colon SW-620 by employing the sulforhodamine B (SRB) assay method. Also all the synthesized compounds tested for in vitro antioxidant and anti-inflammatory activity by using known literature methods. RESULTS: Preliminary in vitro evaluation indicated that most of the compounds 4c, 4d and 4e possess distinct cytotoxicity profile against Colon SW-620 cell line compared to standard drug adriamycin. All the tested compounds showed good to excellent antioxidant activity against one or more reactive (H2O2, DPPH, SOR and NO) radical scavenging species. Additionally, all the synthesized compounds were screened for their in vitro antiinflammatory activity. Compounds 4a, 4b and 4e shows potent anti-inflammatory activity as compared to diclofenac sodium as a standard reference. CONCLUSION: New anti- Colon SW-620 cancer agents are the need of time, we trust that 1-thiocarbamoyl pyrazole derivatives 4c, 4d and 4e constitute an interesting template for the evaluation of new anticancer agent also antioxidant and anti-inflammatory work may provide an interesting insight for further development.