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Cancer is considered one of the leading causes of death globally, especially patients with lung, pancreatic, or brain tumors are most likely to die of cancer, and patients with prostate and breast cancer are at a high risk of noncancer death. As a result, there is ongoing research regarding developing new, safe, and efficient anticancer agents. Coumarin-based naturally occurring compounds possess a broad spectrum of activity in medicinal chemistry, such as anticancer, anti-inflammatory, antimicrobial, antioxidant agents, etc. Many researchers have synthesized coumarinbased novel therapeutic agents via molecular hybridization technique, which offers an excellent opportunity to develop novel compounds with improved biological activities by incorporating two or more pharmacophores. This review aims to shed light on the recent developments of coumarin-based anticancer hybrid derivatives and their Structure-Activity Relationships (SAR). This review serves as a medium that medicinal chemists could utilize to design and synthesize coumarin derivatives with significant pharmacological value as future anticancer agents.

We demonstrate a simple yet efficient one-pot synthesis of two triazolotriazine isomers via DBU mediated Dimroth type rearrangement with excellent yields.

Despite significant advances in understanding cancer pathogenesis, it continues to be one of the leading causes of death. Thus, there is an urgent need for the development of novel, more effective ...

A novel green and efficient catalyst-free, the mild one-pot, multicomponent synthetic strategy has been developed to construct substituted 3,4-dihydro-2H-benzo[b][1,4]oxazine. This reaction proceed...

CDK-1 and CDK-2 are two promising targets for cancer treatment as they are vital in tumor development, proliferation, and apoptosis during the cell cycle process. In treating cancers, CDK inhibitors (small molecules) are used to prevent the overproliferation and overexpression of cancer cells. Consequently, inhibiting CDKs is a promising treatment strategy in oncology. The limitations imposed by current CDK-1 and CDK-2 inhibitors, including neurotoxicity and the development of resistance, have prompted our group to use the novel synthesized pyrazole-thiazole hybrid analogues to investigate their possible potency against CDK-1 and CDK-2. The research study employed detailed computational approaches including molecular docking, molecular dynamics (MD) simulations, post-MD analyses such as RMSD, RMSF, RoG, per-residue energy decomposition, hydrogen bond lifetime analysis, and drug-likeness studies like ADME properties prediction and cytotoxicity, to predict the properties and inhibitory potentials of synthesized pyrazole-thiazole hybrid analogues against CDK-1 and CDK-2. The in silico binding free energy and other analysis reported in the study revealed that four (7 g, 8a, 8b, and 8 h) of the tested molecules against CDK-1 demonstrated a higher binding affinity and structural influence on the target protein than the known inhibitor, Roscovitine (RVT). Similarly, in the case of CDK-2, four (7b, 8a, 8b, and 8f) of the tested compounds showed better results than (RVT). Furthermore, structural examination of the two proteins after binding to the inhibitors revealed that the compounds form stable complexes with the targets and significantly reduced the structural flexibility of the proteins. Therefore, this study suggests the novel pyrazole-thiazole hybrid analogues as potential CDK-1 and CDK-2 inhibitors and could be potential lead compounds for target-based anticancer drugs inhibiting the important proteins, CDK-1 and CDK-2.

Herein we report an efficient one-pot synthesis of [1,2,4]triazolo[1,5

Presently, artemisinin-based combination therapy (ACT) is the first-line therapy of Plasmodium falciparum malaria. With the emergence of malaria parasites that are resistant to ACT, alternative antimalarial therapies are urgently needed. In line with this, we designed and synthesised a series of novel N-(7-chloroquinolin-4-yl)-N’-(4,6-diphenylpyrimidin-2-yl)alkanediamine hybrids (6a-7c) and evaluated their inhibitory activity against the NF54 chloroquine-susceptible strain as a promising class of antimalarial compounds. The antiplasmodial screening revealed that seven analogues showed promising to good activity with half-maximal inhibitory concentration (IC50) = 0.32 μM–4.30 μM. Compound 7a with 1,4-diamine butyl linker and 4-hydroxyl phenyl on fourth and sixth position of pyrimidine core showed the most prominent activity with an IC50 value of 0.32 ± 0.06 μM, with a favourable safety profile of 9.79 to human kidney epithelial (HEK293) cells. The remaining six analogues showed moderate activity with IC50 values ranging from 7.50 μM to 83.01 μM. We further investigated the binding affinities of the molecules to two essential cytosolic P. falciparum heat shock protein 70 homologues; PfHsp70-1 and PfHsp70-z. Compound 7a exhibited the highest binding affinity for both PfHsp70s with KD in a lower nanomolar range (4.4–11.4 nM). Furthermore, molecular docking revealed that compounds 6, 6k, 7b and 7a exhibited better fitness in PfHsp70-1 with compound 7a showing the highest and lowest binding scores of −9.8 kcal/mol. Therefore, we speculate that PfHsp70-1 is one of the targets of these inhibitors. The bioisoteric replacement of the groups at phenyl ring at the fourth and sixth position of the pyrimidine core had a constructive association with antiplasmodial activity. The promising antiplasmodial activity of the synthesised analogues illustrates how crucial molecular hybridisation is as a strategy in the development of quinoline-pyrimidine hybrids as prospective antiprotozoal agents.

A novel green and efficient catalyst-free, mild one-pot, multicomponent synthetic strategy has been developed to construct substituted 3,4-dihydro-2

Parasitic diseases remain a major public health concern for humans, claiming millions of lives annually. Although different treatments are required for these diseases, drug usage is limited due to the development of resistance and toxicity, which necessitate alternative therapies. It has been shown in the literature that parasitic lactate dehydrogenases (LDH) and malate dehydrogenases (MDH) have unique pharmacological selective and specificity properties compared to other isoforms, thus highlighting them as viable therapeutic targets involved in aerobic and anaerobic glycolytic pathways. LDH and MDH are important therapeutic targets for invasive parasites because they play a critical role in the progression and development of parasitic diseases. Any strategy to impede these enzymes would be fatal to the parasites, paving the way to develop and discover novel antiparasitic agents. This review aims to highlight the importance of parasitic LDH and MDH as therapeutic drug targets in selected obligate apicoplast parasites. To the best of our knowledge, this review presents the first comprehensive review of LDH and MDH as potential antiparasitic targets for drug development studies.

SARS-CoV-2 are enveloped positive-stranded RNA viruses that replicate in the cytoplasm. It relies on the fusion of their envelope with the host cell membrane to deliver their nucleocapsid into the host cell. The spike glycoprotein (S) mediates virus entry into cells via the human Angiotensin-converting enzyme 2 (hACE2) protein located on many cell types and tissues' outer surface. This study, therefore, aimed to design and synthesize novel pyrazolone-based compounds as potential inhibitors that would interrupt the interaction between the viral spike protein and the host cell receptor to prevent SARS-CoV 2 entrance into the cell. A series of pyrazolone compounds as potential SARS-CoV-2 inhibitors were designed and synthesized. Employing computational techniques, the inhibitory potentials of the designed compounds against both spike protein and hACE2 were evaluated. Results of the binding free energy from the in-silico analysis, showed that three compounds (7i, 7k and 8f) and six compounds (7b, 7h, 7k, 8d, 8g, and 8h) showed higher and better binding high affinity to SARS-CoV-2 Sgp and hACE-2, respectively compared to the standard drugs cefoperazone (CFZ) and MLN-4760. Furthermore, the outcome of the structural analysis of the two proteins upon binding of the inhibitors showed that the two proteins (SARS-CoV-2 Sgp and hACE-2) were stable, and the structural integrity of the proteins was not compromised. This study suggests pyrazolone-based compounds might be potent blockers of the viral entry into the host cells.

A novel small library of seven fluorinated quinazoline derivatives was synthesized and for four of them, the crystal structures were solved by single X-ray diffractometer and compared the confirmation of molecules in solution-phase using 2D NOESY experiments. Taking advantage of the series prepared, we were able to describe the influence of various substituents on the core scaffold (fluorinated quinazoline) on its molecular conformations’ intermolecular interactions and on the photoluminescent properties. The Hirshfeld surfaces were used to investigate the structure-directing effects of functional groups in controlling their solid-state behavior. Theoretical DFT calculations were carried out for getting additional knowledge on crystal-state interactions as compared to a gas phase. The photo-physical (UV and fluorescence) properties of all compounds have been studied. among the series, five compounds exhibited excellent photoluminescent properties.

A novel series of 4,6-disubstituted pyrazolo[3,4-d]pyrimidines (7-43) bearing various anilines at C-4 position and thiophenethyl or thiopentane moieties at C-6 position have been designed and synthesized by molecular hybridization approach. All the synthesized compounds were evaluated for in vitro CDK2/cyclin E and Abl kinase inhibitory activity as well as anti-proliferative activity against K-562 (chronic myelogeneous leukemia), and MCF-7 (breast adenocarcinoma) cell lines. The structure-activity relationship (SAR) studies revealed that compounds with thiophenethyl group at C-6 with mono-substituted anilines at C-4 exhibited better CDK2 inhibitory activity compared to alkyl group (thiopentane) at C-6 and di-substituted anilines at C-4 of the scaffold. In particular, compounds having 2-chloro, 3-nitro and 4-methylthio aniline groups at C-4 displayed significant enzymatic inhibitory activity against CDK2 with single digit micromolar IC50 values. The in silico molecular docking studies suggested possible binding orientation and the binding energies were in agreement with the observed SAR as well as experimental results. In addition, some of the synthesized compounds showed anti-proliferative effects against K-562 and MCF-7 cancer cell lines with IC50 values in a micromolar range. Thus, the synthesized compounds could be considered as new anticancer hits for further lead optimization.

Department of Chemistry, NIMS University, Sobha Nagar, Jaipur-303 121, Rajasthan, India E-mail : deepakkashyap601@gmail.com, ashima560@gmail.com Department of Chemistry, Meerut College, Meerut-250 001, Uttar Pradesh, India Manuscript received online 05 October 2014, accepted 21 October 2014 An efficient and effective method for the synthesis of 1,3-oxathiolan-5-one derivatives by cyclocondensation reaction at room temperature has been described. This method is an excellent way to obtain the title compounds in quantitative yields in a simple and cost effective way. Applying this methodology, different heterocycles possessing 1,3- oxathiolan-5-one moiety were synthesized.

Department of Chemistry, NIMS University, Shobha Nagar, Jaipur-303 121, Rajasthan, India Department of Chemistry, Meerut College, Meerut-250 001, Uttar Pradesh, India E-mail : narvadeshwarkushwaha@gmail.com, ashima560@gmail.com Manuscript received online 07 September 2014, accepted 15 September 2014 Highly efficient and cost effective cyclocondensation of 2-aminothiophenols/2-aminophenols and carboxylic acids to give benzothiazoles/benzoxazoles has been reported under microwave irradiation condition using pyridine and triphenyl phosphite (TPP). The one pot methodology allowed shorter reaction times, easy isolation of the products and good to excellent yields. The method is practical and efficient for parallel synthesis of the important class of heterocyclic compounds.