Synthesis, anticancer evaluation and in silico studies of novel N‐substituted arylidenethiazolidine‐2,4‐dione derivatives as adenosine monophosphate‐activated protein kinase activators

Posted on 19 March 2024 by

Novel AMPK activator based on N-substituted arylidenethiazolidine-2,4-diones.

Abstract

Design and development of AMP-activated protein kinase (AMPK) activator emerged as a potential therapeutic approach for various types of cancers. In this context, thiazolidine 2,4-dione was invariably found as an important skeleton for the development of new lead compounds. The present study described the synthesis and antitumor evaluation of new hybrids of N-substituted arylidenethiazolidine-2,4-diones as AMPK activators. The in vitro results revealed that several of newly prepared compounds exhibited significant anticancer activity against human prostate cancer (PC3) and breast cancer (MDMB-231) cell growths with IC₅₀ in the range of 2–10 μM. Particularly, molecular hybridization of thiazolidine 2,4-dione with N-2-(4-(trifluoromethyl)phenyl)ethanol and azaindole (compound 16) was the most effective among the series against both PC3 and MDMB-231 cell lines with IC₅₀ 4.28 and 2.5 μM, respectively. Western blot analysis of these thiazolidine 2,4-dione hybrids showed increased (p)-AMPK level in the PC-3 cells indicating direct activation of AMPK. The docking studies at the interface of activator binding site of the AMPK reinforced the in vitro results of potent compounds 13, 16, and 25 having low docking scores −9.0, −9.5, and −9.1 Kcal/mol, respectively.

Formal synthesis of 10‐Hydroxy‐6‐Aryldibenzo[b,g][1,8]Naphthyridin‐11(6H)‐ones from 2‐chloroquinolin‐3‐carbaldehydes and 3‐(Arylamino)cyclohexenones

Posted on 13 March 2024 by

Two component synthesis of naphthyridines.

Abstract

We have described herein a simple and formal synthesis of 10-Hydroxy-6-Aryldibenzo[b,g][1,8]naphthyridin-11(6H)-ones from 2-chloroquinolin-3-carbaldehydes and 3-(Arylamino)cyclohexenones. This protocol provides the formation of four rings including 1,8-naphthyridin under the mild conditions. Furthermore, the cyclohexanone part of the enaminone undergoes air oxidation provided the phenol ring is attached directly to the 1,8-naphthyridin scaffold. These newly formed chemo-types may be useful in drug discovery programs probably as antibacterial agents due to the presence of 1,8-naphthyridine.

Synthesis of a novel fused thieno‐pyrimidine with tetrazole analogs

Posted on 12 March 2024 by

Synthesis of new fused thieno-pyrimidine with tetrazole analogs.

Abstract

This current investigation represents the new series of fused thieno-pyrimidine with synthesized tetrazole analogs (6a–j). Intermediates thieno-[2,3-d]-pyrimidine were prepared by utilizing the Gewald method, and tetrazole (5a–j) was synthesized by [3 + 2] cycloaddition of azide and appropriate nitrile. All the prepared novel molecules were characterized and confirmed by ¹HNMR, ¹³CNMR, LC-MS, and FT-IR spectral analysis.

One pot synthetic approach to 2‐methyl‐5‐phenyl‐7‐amino‐[1,3,4]‐thiadiazolo[3,2‐a]pyrimidine‐6‐carbonitrile derivatives with antifungal evaluation

Posted on 12 March 2024 by

Novel 2-methyl-5-phenyl-7-amino-[1,3,4]-thiadiazolo[3,2-a]pyrimidine-6-carbonitrile derivatives 3 were synthesized from 2-amino-5-methyl-1,3,4-thiadiazole 1 and benzylidinemalononitrile 2 in ethanol by refluxing the mixture with catalytic amount of NaOH. The newly synthesized compounds were also seen as an affective fungicides against Rhizoctonia solani and Trichoderma sp., two fungal microbes causing diseases in rice plants.

Abstract

Novel 2-methyl-5-phenyl-7-amino-[1,3,4]-thiadiazolo[3,2-a]pyrimidine-6-carbonitrile derivatives 3 were synthesized from 2-amino-5-methyl-1,3,4-thiadiazole 1 and benzylidinemalononitrile 2 in ethanol by refluxing the mixture with catalytic amount of NaOH. The structures of all compounds were characterized by elemental analysis, IR, MS, and ¹H nuclear magnetic resonance spectra. The newly synthesized compounds were also seen as an affective fungicide against Rhizoctonia solani and Trichoderma sp., two fungal microbes causing diseases in rice plants.

Ionic liquid‐supported copper‐catalyzed synthesis of 2H‐indazoles under microwave irradiation

Posted on 10 March 2024 by nUpala Dasmahapatra, nKaushik Chanda, nBarnali Maitin

One-pot synthesis of 2H-indazoles under microwave irradiation using an ionic liquid-supported copper-catalyst.

Abstract

Five-membered indazoles are recognized as a special scaffold having a broad spectrum of pharmacological properties among other heterocyclic compounds. New methods must be developed for the effective synthesis of 2H-indazole because of the exceptionally high biological activity of compounds containing a 2H-indazole core. We present the ionic liquid-supported copper-catalyzed one-pot synthesis of 2H-indazoles under microwave irradiation, continuing our ongoing investigation of the potential uses of bioactive compounds produced in the lab. The use of microwave and ionic liquid-supported catalyst makes this process greener and more highly energy efficient than the conventional reported methods. Overall, by forming consecutive C-N and N-N bonds with the help of an ionic liquid-supported copper catalyst, we have developed a novel green one-pot technique for the synthesis of the 2H-indazole motifs in very high yield.

Synthesis of hydantoins from N‐Boc protected amino acid derived amides using polymer‐supported PPh3/CBr4 as a reagent

Posted on 9 March 2024 by

We have developed a mild method to convert N-Boc protected amino acid amides to 3- and 3,5-disubstituted hydantoins.

Abstract

Hydantoin derivatives are versatile structural motifs found in natural products and various compounds with different biological or other properties. Due to their importance in both organic and medicinal chemistry, a number of synthetic procedures have been developed. In this article, a novel methodology utilizing N-Boc protected amino acid amides for their preparation has been described. The cyclisation process was accomplished using solid supported PPh₃ and CBr₄ as reagents affording substituted hydantoins in moderate to good yields (40%–77%).

Amine and nitramine functionalization of imidazole‐triazine and triazole‐triazine skeletons: Exploring for potential multipurpose energetic materials

Posted on 7 March 2024 by nAbhishek Kumar Yadav, nManojkumar Jujam, nVikas D. Ghule, nSrinivas Dharavathn

A set of novel energetic materials (2–7) were designed, synthesized, and thoroughly analyzed, featuring five and six-membered C-C bonded structures that incorporate imidazole-triazine and triazole-triazine frameworks, which displayed balanced energetic properties, stability, and sensitivity.

Abstract

A series of five and six-membered C-C bonded energetic materials (2–7) based on a combination of imidazole-triazine and triazole-triazine backbones were designed, synthesized, and characterized using NMR, IR, Mass spectrometry, and TGA-DSC studies. Further, the structure of compound 4 was supported by single-crystal X-ray analysis. All the newly synthesized energetic compounds exhibit good density, excellent thermal stability, good detonation performance, and low mechanical sensitivity toward impact and friction. Among all, the nitrate salt 4 exhibits balanced properties, including high density (1.80 g cm⁻³), excellent thermal stability (254°C), good detonation velocity (8178 m s⁻¹), and low sensitivity towards impact and friction. The facile synthetic feasibility, thermal stability, energetic performance, and insensitivity of all the molecules suggest they can be used as an insensitive secondary explosive in various defense and civilian applications.

Issue Information

Posted on 7 March 2024 by Wiley: Journal of Heterocyclic Chemistry: Table of Contents

Journal of Heterocyclic Chemistry, Volume 61, Issue 3, Page 397-400, March 2024.

One‐pot green synthesis, study of fluorescence properties, and biological activity of pyrano[3,2‐c]chromenes derivatives via mesoporous materials MgO/SBA‐15

Posted on 7 March 2024 by

One-pot green synthesis, study of fluorescence properties, and biological activity of pyrano[3,2-c]chromenes derivatives via mesoporous materials MgO/SBA-15.

Abstract

This current work describes the preparation of MgO-SBA-15 catalysts by ultrasonic method, and it is characterized by the different analysis techniques of XRD, BET, SEM, and IRTF. In order to find out an application for this mesoporous material, MgO/SBA-15 was used as a heterogeneous catalyst in the one-pot synthesis of pyrano[3,2-c]chromenes derivatives isolated at room temperature reaction according to green chemistry criteria. To enhance these derivatives, a spectroscopic study of molecular fluorescence properties was carried out as well as an identification analysis by nuclear magnetic resonance and FTIR was used. Furthermore, biological activity experiment is also carried out, from where the obtained test results were satisfactory for AC09, AC05, and AC10 compounds and they are checked after computation by molecular modeling.

Dearomative [4 + 2] cycloaddition of 3‐nitroindoles with ortho‐amino Morita−Baylis−Hillman carbonates to forge indole‐fused quinolines

Posted on 7 March 2024 by

A dearomative [4 + 2] cycloaddition of 3-nitroindoles ortho-amino Morita−Baylis−Hillman carbonates was established under mild conditions.

Abstract

A dearomative [4 + 2] cycloaddition of 3-nitroindoles ortho-amino Morita−Baylis−Hillman carbonates was established under mild conditions. This method provides an efficient and practical approach for delivering tetrahydro-5H-indolo[2,3-b]quinolines containing three contiguous stereocenters, two tertiary and one quaternary, in high yield (up to 95%) with excellent diastereoselectivity (all cases >25:1 dr). The potential synthetic applications of this strategy were also highlighted by the scale-up experiment and further synthetic transformation. Moreover, the structure and relative configuration of the cycloadduct was unequivocally confirmed by single-crystal X-ray diffraction.