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Phosphorus oxychloride, POCl3, an important phosphorus compound, has diverse applications in synthetic chemistry. It plays an important role in chlorination, Vilsmeier Haack reaction, dehydration and cyclization which have been highlighted here. Moreover, different reaction conditions implied and reported in the literature along with the general mechanism are provided briefly in this review. This review provides an insight into the recent applications of phosphorus oxychloride as a reagent in organic syntheses in the last two year i.e. 2018–19. [ABSTRACT FROM AUTHOR]

Objective: To investigate the effects of Alogliptin in chemical-induced post-menopausal osteoporosis., Methodology: The binding affinity of alogliptin with osteogenic proteins was analysed in silico. The effect of alogliptin on osteogenic proteins and mineralization of osteoblastic cells was evaluated in UMR-106 cells. Further, in vivo anti-osteoporotic activity of alogliptin was evaluated in postmenopausal osteoporosis. Various bone turnover markers were assayed in serum. This followed the analysis of microarchitecture of bone, histology, and immunohistochemistry (IHC) of bone tissue., Results: Docking scores showed that alogliptin has binding affinity for bone alkaline phosphatase (BALP), osteocalcin, and bone morphogenic protein (BMP-2). Alogliptin also enhanced mineralization of osteoblast cells, evidenced with increased ALP, osteocalcin, and BMP-2. Animal studies revealed significant elevation of bone formation markers, bone ALP, osteocalcin and BMP-2, and decreased bone resorption markers, receptor activator of NF-κβ (RANKL), cathepsin K (CTSK), tartrate resistant acid phosphatase (TRAcP5b) in VCD-induced post-menopausal osteoporosis. Micro computed tomography (μCT) analysis and histology of femur bone and lumbar vertebrae demonstrated decrease in trabecular separation and improved bone density. IHC of femur showed reduced DPP4 enzyme., Conclusions: Alogliptin increased mineralization in osteoblast cells. It had beneficial effects also altered bone turnover markers, repaired the trabecular microstructure, improved bone mineral density, and exhibited bone forming capacity targeting DPP-4 enzyme in postmenopausal osteoporosis., (© The Author(s) 2024. Published by Oxford University Press on behalf of the Royal Pharmaceutical Society. All rights reserved. For commercial re-use, please contact reprints@oup.com for reprints and translation rights for reprints. All other permissions can be obtained through our RightsLink service via the Permissions link on the article page on our site—for further information please contact journals.permissions@oup.com.)

Cancer bears a significant share of global mortality. The enzyme Lysine Specific Demethylase 1 (LSD1, also known as KDM1A), since its discovery in 2004, has captured the attention of cancer researchers due to its overexpression in several cancers like acute myeloid leukaemia (AML), solid tumours, etc. The Lysine Specific Demethylase (LSD1) downregulation is reported to have an effect on cancer proliferation, migration, and invasion. Therefore, research to discover safer and more potent LSD1 inhibitors can pave the way for the development of better cancer therapeutics. These efforts have resulted in the synthesis of many types of derivatives containing diverse structural nuclei. The present manuscript describes the role of Lysine Specific Demethylase 1 (LSD1) in carcinogenesis, reviews the LSD1 inhibitors explored in the past five years and discusses their comprehensive structural activity characteristics apart from the thorough description of LSD1. Besides, the potential challenges, opportunities, and future perspectives in the development of LSD1 inhibitors are also discussed. The review suggests that tranylcypromine derivatives are the most promising potent LSD1 inhibitors, followed by triazole and pyrimidine derivatives with IC₅₀ values in the nanomolar and sub-micromolar range. A number of potent LSD1 inhibitors derived from natural sources like resveratrol, protoberberine alkaloids, curcumin, etc. are also discussed. The structural-activity relationships discussed in the manuscript can be exploited to design potent and relatively safer LSD1 inhibitors as anticancer agents., (Copyright© Bentham Science Publishers; For any queries, please email at epub@benthamscience.net.)

Background: Histone deacetylases (HDACs) play a vital role in the epigenetic regulation of transcription and expression. HDAC1 overexpression is seen in many cancers. Methodology: The authors synthesized and evaluated 27 novel coumarin-based amide derivatives for HDAC1 inhibitory activity. The compounds were screened at the US National Cancer Institute, and 5k and 5u were selected for five-dose assays. Compound 5k showed GI 50 values of 0.294 and 0.264 μM against MOLT-4 and LOX-IMVI, respectively; whereas 5u had GI 50 values of 0.189 and 0.263 μM, respectively. Both derivatives showed better activity than entinostat and suberoylanilide hydroxamic acid. Compound 5k exhibited an IC 50 value of 1.00 μM on ACHN cells. Conclusion: Coumarin derivatives exhibited promising HDAC1 inhibitory potential and warrant future development as anticancer agents.

Cancer is one of the severe diseases in which abnormal cells divide and proliferate in an uncontrolled manner without any regulation. Globally cancer is among the leading causes of death; according to a recent report of by the WHO, around 10 million people died in 2018 due to cancer. It has also been reported that by 2040, approximately 30 million new cases will be reported every year. The increase in the incidences of cancer is taking a toll on the health care system worldwide. Considerable scientific literature is available on anticancer agents but newer therapeutic strategies are still required in this field to address novel approaches to drug design and discovery to counter this problem. Imidazothiazole represents a privileged scaffold in medicinal chemistry and provides the medicinal chemist the possibility to modulate the physiochemical properties of the lead compound. In recent times, imidazothiazole scaffold is broadly explored for its anticancer activity, which acts through various mechanisms such as EGFR, B-RAF, DHFR kinase inhibition and tubulin polymerization inhibition and other molecular mechanisms of action. Due to their feasible synthetic accessibility and promising pharmacological profile, it has attracted various medicinal chemists to explore and develop imidazothiazole derivatives as potent and safe anticancer agents. In the present article, we have reviewed various potent imidazothiazole scaffold-based derivatives reported as anticancer agents, their synthetic strategies, Structure Activity Relationship (SAR), mechanism of action, and molecular docking along with their future perspective. This review will be very useful for medicinal chemists for drug design and development of imidazothiazole-based potent antiproliferative agents., (Copyright© Bentham Science Publishers; For any queries, please email at epub@benthamscience.net.)

Coronavirus disease (COVID-19) was reported to be transmitted from bats to humans and, became a pandemic in 2020. COVID-19 is responsible for millions of deaths worldwide and still, the numbers are increasing. Further, despite the availability of vaccines, mutation in the virus continuously poses a threat of re-emergence of the more lethal form of the virus. So far, the repurposing of drugs has been exercised heavily for the identification of therapeutic agents against COVID-19, which led FDA to approve many drugs for the same e.g., remdesivir, favipiravir, ribavirin, etc. The anti-COVID drugs explored via other approaches include nirmatrelvir (used in combination with ritonavir as Paxlovid), tixagevimab and cilgavimab (both used in combination with each other) and others. However, these approved drugs failed to achieve a significant clinical outcome. Globally, natural bioactive have also been explored for anti-COVID-19 effects, based on their traditional medicinal values. Although the clinical findings suggest that FDA-approved drugs and natural bioactives can help reducing the overall mortality rate but the significant clinical outcome was not achieved. Therefore, the focus has been shifted towards new drug development. In line with that, a lot of work has been done and still going on to explore heterocyclic compounds as potent anti- COVID-19 drugs. Several heterocyclic scaffolds have been previously reported with potent antiinflammatory, anticancer, anti-viral, antimicrobial and anti-tubercular effects. Few of them are under consideration for clinical trials whereas others are under preclinical investigation. Hence, this review discusses the evidence of rationally designed and tested heterocyclic compounds acting on different targets against COVID-19. The present article will help the researches and will serve as a pivotal resource in the design and development of novel anti-COVID-19 drugs., (Copyright© Bentham Science Publishers; For any queries, please email at epub@benthamscience.net.)

A series of novel cyanopyrimidine-hydrazone hybrids were synthesized and characterized with various spectroscopic techniques. The synthesized compounds were tested at NCI, USA, on a 60-cell line panel and most of the compounds showed remarkable cytotoxic activity against different cancer cell lines. Compound 5a was found to be the most potent compound of the series and it was further selected for five dose assays wherein it exhibited GI 50 value of 0.414 µM and 0.417 µM against HOP-62 and OVCAR-4 cell lines respectively. The in-silico mechanistic studies indicated that these compounds are acting through inhibition of lysine specific demethylase 1 (LSD1) as evident from in to vitro LSD1 inhibition activity of compounds. Among various synthesized derivatives, compound 5a was found to have IC50-value of 0.956 µM. In addition, absorption, distribution, metabolism, excretion and toxicity profile (ADMET) was assessed for these novel derivatives to get an insight on their pharmacokinetic/dynamic attributes which revealed that synthesized compounds showed acceptable metabolic stability in human liver microsomes with minimal inhibition of cytochrome P450s (CYPs). The results indicated that compound 5a could be a promising lead compound for further development as a therapeutic agent for anticancer activity., (Copyright © 2022 Elsevier Inc. All rights reserved.)

'Epigenetic' regulation of genes via post-translational modulation of proteins is a wellexplored approach for disease therapies, particularly cancer chemotherapeutics. Histone deacetylases (HDACs) are one of the important epigenetic targets and are mainly responsible for balancing the acetylation/deacetylation of lysine amino acids on histone/nonhistone proteins along with histone acetyltransferase (HAT). HDAC inhibitors (HDACIs) have become important biologically active compounds for the treatment of cancers due to cell cycle arrest, differentiation, and apoptosis in tumor cells, thus leading to anticancer activity. Out of the four classes of HDAC, i.e., Class I, II, III, and IV, HDACIs act on Class IV (Zinc dependent HDAC), and various FDA-approved drugs belong to this category. The required canonical pharmacophore model (zinc-binding group, surface recognition cap, and appropriate linker) supported by HDACIs, various heterocyclic moieties containing compounds exhibiting HDAC inhibitory activity, and structure-activity relationship of different synthetic derivatives reported during the last twelve years have been summarized in this review., (Copyright© Bentham Science Publishers; For any queries, please email at epub@benthamscience.net.)

In continuation of our previous work on cancer and inflammation, 15 novel pyrazole-pyrazoline hybrids (WSPP1-15) were synthesized and fully characterized. The formation of the pyrazoline ring was confirmed by the appearance of three doublets of doublets in 1 H nuclear magnetic resonance spectra exhibiting an AMX pattern for three protons (H A , H M , and H X ) of the pyrazoline ring. All the synthesized compounds were screened for their in vitro anticancer activity against five cell lines, that is, MCF-7, A549, SiHa, COLO205, and HepG2 cells, using the MTT growth inhibition assay. 5-Fluorouracil was taken as the positive control in the study. It was observed that, among them, WSPP11 was found to be active against A549, SiHa, COLO205, and HepG2 cells, with IC 50 values of 4.94, 4.54, 4.86, and 2.09 µM. All the derivatives were also evaluated for their cytotoxicity against HaCaT cells. WSPP11 was also found to be nontoxic against normal cells (cell line HaCaT), with an IC 50 value of more than 50 µM. The derivatives were also evaluated for their in vitro anti-inflammatory activity by the protein (egg albumin) denaturation assay and the red blood cell membrane stabilizing assay, using diclofenac sodium and celecoxib as standard. Compounds that showed significant anticancer and anti-inflammatory activities were further studied for COX-2 inhibition. The manifestation of a higher COX-2 selectivity index of WSPP11 as compared with other derivatives and an in vitro anticancer activity against four cell lines further established that compounds that were more selective toward COX-2 also exhibited a better spectrum of activity against various cancer cell lines., (© 2020 Deutsche Pharmazeutische Gesellschaft.)

In continuation of our previous work on anticancer and anti-inflammatory agents, a series of 22 novel methylene-bearing sulfur-containing cyanopyrimidine derivatives was synthesized by Biginelli condensation reaction, which was followed by nucleophilic substitution of the chloro group with secondary or tertiary amines. Structural confirmation of these derivatives was attained through different spectral techniques. Then, anticancer evaluation of these compounds was done at the National Cancer Institute. Compounds 4g, 4j, 4k, and 4v demonstrated appreciable results against different cell lines. Among the synthesized compounds, 4g (NSC: 795475) exhibited a growth inhibition (GI) of 81.34% against the NCI-H460 lung cancer cell line, 72.64% against the ACHN renal cancer cell line, and 112.17% against the OVCAR-4 ovarian cancer cell line. Compound 4j (NSC: 795746) was active against U-251 CNS cancer, OVCAR-4 ovarian cancer, and 786-0 and ACHN renal cancer cell lines, with GI of 78.84%, 150.38%, 75.64%, and 86.45%, respectively. The literature supporting the association between cancer and underlying inflammation prompted us to evaluate the four compounds, 4g, 4j, 4k, and 4v, with appreciable anticancer activity for their in vitro anti-inflammatory activity. Cyclooxygenase (COX)-2 inhibition studies were also performed to study the molecular target. To validate the target study, molecular docking studies in the ligand-binding domain of COX-2 (PDB ID: 1CX2) were also performed. Compounds 4g, 4j, and 4k did not show cytotoxicity on RAW 264.7 cells up to 10 μM concentration; however, compound 4v showed cytotoxic effects at 10 μM concentration., (© 2020 Deutsche Pharmazeutische Gesellschaft.)

Inhibition of dihydrofolate reductase from Mycobacterium tuberculosis-dihydrofolate reductase (Mtb-DHFR) has emerged as a promising approach for the treatment of tuberculosis. To identify novel Mtb-DHFR inhibitors, structure-based virtual screening (SBVS) of the Molecular Diversity Preservation International (MolMall) database was performed using Glide against the Mtb-DHFR and h-DHFR enzymes. On the basis of SBVS, receptor fit, drug-like filters, and ADMET (absorption, distribution, metabolism, excretion, and toxicity) analysis, 16 hits were selected and tested for their antitubercular activity against the H 37 R V strain of M. tuberculosis. Five compounds showed promising activity with compounds 11436 and 15275 as the most potent hits with IC 50 values of 0.65 and 12.51 μM, respectively, against the H 37 R V strain of M. tuberculosis. The two compounds were further tested in the Mtb-DHFR and h-DHFR enzymatic assay for selectivity and were found to be three- to eight-fold selective towards Mtb-DHFR over h-DHFR with minimum inhibitory concentration values of 5.50, 73.89 µM and 42.00, 263.00 µM, respectively. In silico simulation studies also supported the stability of the protein-ligand complex formation. The present study demonstrates the successful utilization of in silico SBVS tools for the identification of novel and potential Mtb-DHFR inhibitors and compound 11436 ((2,4-dihydroxyphenyl)(3,4,5-trihydroxyphenyl)methanone) as a potential lead for the development of novel Mtb-DHFR inhibitors., (© 2019 Deutsche Pharmazeutische Gesellschaft.)

Introduction : Combretastatins represent a potent class of phenolic-stilbene natural products that function as colchicine binding site inhibitors of tubulin polymerization and have been advanced as promising anticancer lead compounds. Among them, combretastatin A-4 is the most potent lead molecule due to its broad spectrum cytotoxicity against a variety of tumors. However, low water solubility due to its high lipophilic nature and inter-conversion of olefinic double bond from more active cis to less active trans- conformation poses limitations to its clinical utility. However, different approaches including prodrugs, salt formations, structural modifications, prevention of inter-conversion of the olefinic bond and changes to the substitution pattern on the rings of combretastatin A-4 were investigated and successfully resulted in different combretastatin-based molecules that demonstrated varying levels of potency against different types of tumors during their in-vitro and in-vivo studies. Areas covered : This review covers the patents over a period of 2008-2018. Expert opinion : Molecular hybridization and prodrug designing imparted multi-targeted actions to combretastatin derivatives. Currently, various combretastatin derivatives are under clinical trials. These derivatives could be used to treat disorders other than cancer, due to their vascular disrupting action.

In continuance with earlier reported work, an extension has been carried out by the same research group. Mulling over the ongoing condition of resistance to existing antimalarial agents, we had reported synthesis and antimalarial activity of certain pyrazole-1,3,4-oxadiazole hybrid compounds. Bearing previous results in mind, our research group ideated to design and synthesize some more derivatives with varied substitutions of acetophenone and hydrazide. Following this, derivatives 5a-r were synthesized and tested for antimalarial efficacy by schizont maturation inhibition assay. Further, depending on the literature support and results of our previous series, certain potent compounds (5f, 5n and 5r) were subjected to Falcipain-2 inhibitory assay. Results obtained for these particular compounds further strengthened our hypothesis. Here, in this series, compound 5f having unsubstituted acetophenone part and a furan moiety linked to oxadiazole ring emerged as the most potent compound and results were found to be comparable to that of the most potent compound (indole bearing) of previous series. Additionally, depending on the available literature, compounds (5a-r) were tested for their antileishmanial potential. Compounds 5a, 5c and 5r demonstrated dose-dependent killing of the promastigotes. Their IC 50 values were found to be 33.3 ± 1.68, 40.1 ± 1.0 and 19.0 ± 1.47 μg/mL respectively. These compounds (5a, 5c and 5r) also had effects on amastigote infectivity with IC 50 of 44.2 ± 2.72, 66.8 ± 2.05 and 73.1 ± 1.69 μg/mL respectively. Further target validation was done using molecular docking studies. Acute oral toxicity studies for most active compounds were also performed., (Copyright © 2019 Elsevier Inc. All rights reserved.)

In the present study, a series of dibenzepinones, dibenzoxepines, and benzosuberones targeting p38α MAP kinase were subjected to pharmacophore modelling, 3D-QSAR and molecular docking studies. The IC 50 values for these 67 compounds ranged between 0.003 and 6.80 μM. A five-point model (DDHHR.8) was generated using these compounds. This model was found to be statistically significant and was found to have high correlation (R 2  = 0.98), cross-validation coefficient (Q 2  = 0.95) and F (330) values at six component PLS factor. Tests were performed to ascertain the efficacy of the generated model. These tests included external validation, Tropsha's test for predictive ability, Y-randomisation test and domain of applicability (APD). In order to check the restrictivity of the model, enrichment studies were performed with inactive compounds by using decoy set molecules. To evaluate the effectiveness of the docking protocol, the co-crystallised ligand was extracted from the ligand-binding domain of the protein and was re-docked into the same position. Both the conformers were then superimposed, suggesting satisfactory docking parameters with an RMSD value of less than 1.0 Å (0.853 Å). A 10 ns molecular dynamics simulation confirmed the docking results of the 3UVP-ligand complex and the presumed active conformation. The outcome of the present study provides insight into the molecular features that promote bioactivity and can be exploited for the prediction of novel potent p38α MAP kinase inhibitors before carrying out their synthesis and anticancer evaluation., (Copyright © 2019 Elsevier Ltd. All rights reserved.)

Meagre and suboptimal therapeutic response along with the side effect profile associated with the existing anticancer therapy have necessitated the development of new therapeutic modalities to curb this disease. Bearing in mind the current scenario, a series of 1,2,3-triazole linked 3-(1,3-diphenyl-1H-pyrazol-4-yl)acrylates was synthesized following a multi-step reaction scheme. Initial screening for anticancer potential was done by in vitro sulforhodamine B assay against four human cancer cell lines- MCF-7 (breast), A549 (Lung) and HCT-116 and HT-29 (Colon). On evaluation, several compounds showed promising growth inhibition against all the cell lines, particularly compounds 6e, 6f and 6n. Among them, compound 6f displayed IC 50 values of 1.962, 3.597, 1.764 and 4.496 µM against A549, HCT-116, MCF-7 and HT-29 cell lines respectively. Furthermore, the apoptosis inducing potential of the compounds was determined by Hoechst staining and DNA fragmentation assay. Colony formation inhibition assay was also carried out to determine the long term cytotoxic potential of the molecules. Moreover, compounds 6e, 6f and 6n were also evaluated for anti-inflammatory activity by protein albumin denaturation assay and red blood cell membrane stabilizing assay., (Copyright © 2019 Elsevier Inc. All rights reserved.)

Morpholine, a six-membered heterocycle containing one nitrogen and one oxygen atom, is a moiety of great significance. It forms an important intermediate in many industrial and organic syntheses. Morpholine containing drugs are of high therapeutic value. Its wide array of pharmacological activity includes anti-diabetic, anti-emetic, growth stimulant, anti-depressant, bronchodilator and anticancer. Multi-drug resistance in cancer cases have emerged in the last few years and have led to the failure of many chemotherapeutic drugs. Newer treatment methods and drugs are being developed to overcome this problem. Target based drug discovery is an effective method to develop novel anticancer drugs. To develop newer drugs, previously reported work needs to be studied. Keeping this in mind, last five year's literature on morpholine used as anticancer agents has been reviewed and summarized in the paper herein., (Copyright © 2019 Elsevier Masson SAS. All rights reserved.)

The quinoline core possesses a vast number of biological activities such as anticancer, antimalarial, antimicrobial, antifungal, antitubercular and antileishmanial. The conventional classical synthetic methods require the use of expensive and harsh conditions such as high temperature. Currently the scientific communities are searching new methodology to eliminate the use of chemicals, solvents and catalysts, which are hazardous to human health as well as to environment. This review provides a concise overview of new dimensions of green chemistry approaches in designing quinoline scaffold that would encourage the researchers towards green chemistry as well as future application of these greener, non-toxic, environment friendly methods in designing quinoline scaffold., (Copyright © 2018 Elsevier Masson SAS. All rights reserved.)

1,3,4-Oxadiazole, a five-membered aromatic ring can be seen in a number of synthetic molecules. The peculiar structural feature of 1,3,4-oxadiazole ring with pyridine type of nitrogen atom is beneficial for 1,3,4-oxadiazole derivatives to have effective binding with different enzymes and receptors in biological systems through numerous weak interactions, thereby eliciting an array of bioactivities. Research in the area of development of 1,3,4-oxadiazole-based derivatives has become an interesting topic for the scientists. A number of 1,3,4-oxadiazole based compounds with high therapeutic potency are being extensively used for the treatment of different ailments, contributing to enormous development value. This work provides a systematic and comprehensive review highlighting current developments of 1,3,4-oxadiazole based compounds in the entire range of medicinal chemistry such as anticancer, antifungal, antibacterial, antitubercular, anti-inflammatory, antineuropathic, antihypertensive, antihistaminic, antiparasitic, antiobesity, antiviral, and other medicinal agents. It is believed that this review will be of great help for new thoughts in the pursuit for rational designs for the development of more active and less toxic 1,3,4-oxadiazole based medicinal agents., (Copyright© Bentham Science Publishers; For any queries, please email at epub@benthamscience.net.)

Malaria, an upsetting malaise caused by a diverse class of Plasmodium species affects about 40% of the world's population. The distress associated with it has reached colossal scales owing to the development of resistance to most of the clinically available agents. Hence, the search for newer molecules for malaria treatment and cure is an incessant process. After the era of a single molecule for malaria treatment ended, there was an advent of combination therapy. However, lately there had been reports of the development of resistance to many of these agents as well. Subsequently, at present most of the peer groups working on malaria treatment aim to develop novel molecules, which may act on more than one biological processes of the parasite life cycle, and these scaffolds have been aptly termed as Hybrid Molecules or Double Drugs. These molecules may hold the key to hitherto unknown ways of showing a detrimental effect on the parasite. This review enlists a few of the recent advances made in malaria treatment by these hybrid molecules in a sequential manner., (Copyright© Bentham Science Publishers; For any queries, please email at epub@benthamscience.net.)