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Background: Quinoline is considered to be a privileged heterocyclic ring owing to its presence in diverse scaffolds endowed with promising activity profiles. In particular, quinoline containing compounds have exhibited substantial antiproliferative effects through the diverse mechanism of actions, which indicates that the heteroaryl unit is flexible as well as accessible to subtle structural changes that enable its inclusion in chemically distinct anti-tumor constructs. Methods: Herein, we describe a medicinal chemistry perspective on quinolines as anticancer agents by digging into the peer-reviewed literature as well as patents published in the past few years. Results: This review will serve as a guiding tool for medicinal chemists and chemical biologists to gain insights about the benefits of quinoline ring installation to tune the chemical architectures for inducing potent anticancer effects. Conclusion: Quinoline ring containing anticancer agents presents enough optimism and promise in the field of drug discovery to motivate the researchers towards the continued explorations on such scaffolds. It is highly likely that adequate efforts in this direction might yield some potential cancer therapeutics in the future.

This paper introduces reverse patterning lithography (RPL), which combines microcontact printing (μCP) of a custom-designed fluorinated adsorbate on gallium arsenide (GaAs) and the deposition of a ...

Xanthine oxidase (XO) is a molybdoflavoprotein that catalyzes the oxidative hydroxylation of purines to produce uric acid and reactive oxygen species. These reaction products can cause severe disease conditions like hyperuricemia which makes XO enzyme, an important therapeutic target in diseases like gout.Herein, patents from 2015 to 2020 are discussed to disclose the synthetic, as well as natural compounds, claimed to inhibit XO enzyme. The article also presents the last five years of clinical progression of some prominent XO inhibitors.There has been considerable creativity in the discovery of novel XO inhibitors in the last five years that falls outside the purine scaffold. Along with the evaluation of synthetic compounds, natural compounds can also be an area of interest for the discovery of novel XO inhibitors. Based on the patent literature of last five years, we can expect a burst of novel alternate compounds in the near future which could have the ability to reduce the uric acid level, by inhibiting XO enzyme in patients, which at the moment are striving hard to fight against the dreadful disease condition like gout.

Clayware membrane amalgamated with 20% montmorillonite (M-20), acts as an excellent cost effective proton exchange membrane (PEM) for the application in field-scale microbial fuel cells (MFCs). In this investigation, M-20 membrane was pre-treated by acid (M-A), neutral water (M-N) and alkali (M-B), followed by the determination of the membrane properties to access their applicability in MFCs. With alkali treatment of M-20 membrane, maximum proton mass transfer coefficient of 6 × 10−6 cm s−1 was obtained, which was nearly five times higher than M-A (1.15 × 10−6 cm s−1) and four times higher than the control membrane, M-N. Proton conductivity was also found to be maximum for M-B (17.9 × 10−3 S cm−1), which was four times higher than both M-N (4.4 × 10−3 S cm−1) and M-A (4.6 × 10−3 S cm−1). Oxygen mass transfer coefficient was found to be minimum for M-B (4.02 × 10−5 cm s−1), which was considerably lesser than that observed for M-N (16.2 × 10−5 cm s−1) and M-A (13.8 × 10−5 cm s−1). Cation transport number of M-B (0.15 ± 0.01) was found to be two folds lower than M-N, demonstrating M-B is more selective towards proton transport compared to other cations. The MFC-B with M-B as PEM performed superior as compared with other MFCs, demonstrating coulombic efficiency (CE) of 10.2%, chemical oxygen demand (COD) removal efficiency of 88% and power density of 83.5 mW m−2. On the other hand, MFCs using M-A and M-N as PEM, demonstrated mediocre performance with CE of 6% and 7.6%, COD removal efficiency of 80% and 83% and power density of 40.4 ± 6.2 mW m−2 and 64.0 ± 5.8 mW m−2, respectively. Hence, alkali treatment of clayware ceramic membrane elucidated its appropriateness for proliferating the efficacy of MFCs and these are recommended for scaling up of MFCs.

Keeping in view the successive attributes of benzodiazepines on the central nervous system, we have synthesized a novel series of benzodiazepine derivatives as antioxidant and anxiolytic agents. All the compounds were obtained in good yield by facile synthesis. To check their antioxidant potential, DPPH (2,2-diphenyl-1-picrylhydrazyl) free radical scavenging assay was performed. Among all the synthetics seven derivatives (SD-3, SD-5, SD-7, SD-14, SD-18, SD-19, and SD-20) exhibited IC50 values ranging from 76 to 489 nM. These seven compounds were further evaluated to check their binding abilities towards the benzodiazepine binding site on GABAA receptors. Three best-fit ligands (SD-3, SD-14 and SD-20) were further evaluated for their anxiolytic effect by using three in vivo mice models i.e. Elevated Plus Maze, Light & Dark box, and Mirror Chamber model. The study revealed that compounds SD-3 and SD-20 showed the best anxiolytic effect as compared to standard drug diazepam even at an oral dose of 1.0 mg/kg.

Keeping in view various pharmacological attributes of curcumin, coumarin, and isatin derivatives, triazole-tethered monocarbonyl curcumin-coumarin and curcumin-isatin molecular hybrids have been synthesized and evaluated for their antibacterial potential against Gram-positive (Enterococcus faecalis and Staphylococcus aureus) and Gram-negative (Pseudomonas aeruginosa and Escherichia coli) human pathogenic bacterial strains. Among all hybrid molecules, A-4 and B-38 showed the most potent antibacterial activity with inhibition zones of 29 and 31 mm along with MIC values of 12.50 and 6.25 μg/mL, respectively. Structure-activity relationship that emerged from biological data revealed that the two-carbon alkyl chain between triazole and coumarin/isatin moiety is well tolerable for the activity. Bromo substitution at the fifth position of isatin, para-cholo substitution in the case of curcumin-isatin, and para-methoxy in the case of curcumin-coumarin hybrids on ring A of curcumin are most suitable groups for the antibacterial activity. Various types of binding interactions of A-4 and B-38 within the active site of dihydrofolate reductase (DHFR) of S. aureus are also streamlined by molecular modeling studies, suggesting their capability in completely blocking DHFR.

Keeping in view various pharmacological attributes of indole and coumarin derivatives, a new series of indolindione–coumarin molecular hybrids was rationally designed and synthesized. All synthesized hybrid molecules were evaluated for their antimicrobial potential against Gram-negative bacterial strains (Escherichia coli and Salmonella enterica), Gram-positive bacterial strains (Staphylococcus aureus and Mycobacterium smegmatis), and four fungal strains (Candida albicans, Alternaria mali, Penicillium sp., and Fusarium oxysporum) by using the agar gel diffusion method. Among all synthetics, compounds K-1 and K-2 were found to be the best antimicrobial agents with the minimum inhibitory concentration values of 30 and 312 μg/mL, against Penicillium sp. and S. aureus, respectively. The biological data revealed some interesting facts about the structure–activity relationship which state that the electronic environment on the indolinedione moiety and carbon chain length between indolinedione and triazole moieties considerably affect the antimicrobial potential of the synthesized hybrids. Various types of binding interactions of K-2 within the active site of S. aureus dihydrofolate reductase were also streamlined by molecular modeling studies, which revealed the possible mechanism for potent antibacterial activity of the compound.

Epitaxial lift-off (ELO) is an efficient method to greatly reduce the cost of GaAs photovoltaics without sacrificing their performance. However, the use of strong acids to remove the sacrificial layer in the conventional ELO method restricts the reusability of the substrate and adds extra substrate polishing costs. Here, we report a novel method of using a water-dissolvable ‘NaCl’ sacrificial layer which provides the advantage of repeated reusability of GaAs wafers without any substrate polishing costs. Good-quality epitaxial GaAs has been grown on NaCl sacrificial layer. Atomic Force Microscopy results show very smooth GaAs wafer after epitaxial liftoff.

Two series of benzoflavone derivatives were rationally designed, synthesized and evaluated for their xanthine oxidase (XO) inhibitory potential. Among both series, eight compounds (NF-2, NF-4, NF-9, NF-12, NF-16, NF-25, NF-28, and NF-32) were found to exert significant XO inhibition with IC(50) values lower than 10 μM. Enzyme kinetic studies revealed that the most potent benzoflavone derivatives (NF-4 and NF-28) are mixed type inhibitors of the XO enzyme. Molecular modeling studies were also performed to investigate the binding interactions of these molecules (NF-4 and NF-28) with the amino acid residues present in the active site of the enzyme. Docking results confirmed that their favorable binding conformations in the active site of XO can completely block the catalytic activity of the enzyme. Benzoflavone derivatives exhibiting potent XO enzyme inhibition also showed promising results in a hyperuricemic mice model when tested in vivo.

International audience; We synthesized affinity-based chemical probes of cytosine-adenosine bisubstrate analogs and identified several potential targets by proteomic analysis. The validation of the proteomic analysis identified the chemical probe as a specific inhibitor of glucose-regulated protein 94 (GRP94), a potential drug target for several types of cancers. Therefore, as a result of the use of bisubstrate-type chemical probes and a chemical-biology methodology, this work opens the way to the development of a new family of GRP94 inhibitors that could potentially be of therapeutic interest.

Most of the anti-inflammatory drugs in clinical practice are becoming outdated owing to their potential side and adverse effects. These are found to be highly unsafe for long term use. Thus, since last few years, new anti-inflammatory agents are being developed and number of them are in advanced stages of clinical trials. Heterocyclic molecules have gained great attention of chemists due to their similarity to different biological precursors. In the current review, we have highlighted the recent developments (2015 onwards) in designing and synthesis of various heterocyclic anti-inflammatory molecules along with detailed SAR studies. The principal objective of this review is to provide a profound overview of the recently explored heterocyclic anti-inflammatory agents belonging to various classes such as pyrazole, pyrimidine, benzimidazole, indole, and other related heterocyclic compounds. In addition, an enlarged view on potential interactions of synthetic preparations with target inflammatory enzymes or cytokines has been provided. We have also enlisted lead compounds undergoing different clinical trials against inflammation. The elementary aim of this review is to provide restructured knowledge regarding heterocyclic molecules which will be valuable for the scientists working in the field of anti-inflammatory chemistry. The authors believe that lead compounds mentioned in the report will help to design and develop novel anti-inflammatory drug molecules targeting various factors involved in the progression of inflammation.

BACKGROUND Esterase is an enzyme that splits esters into an acid and alcohol. Varieties of esterases are present in human body to control diverse set of cellular processes and execute their specific functions. It can be seen that any increase in metabolites produced by these enzymes lead to severe pathological conditions like Alzheimer disease, hypercholesterolemia etc. Objective: Numerous esterase inhibitors have been developed and reported by the researchers around the globe, but not systematically summarized yet. Therefore, this assemblage focuses on various reported esterase inhibitors during recent past with detailed account of the design strategies employed for the synthesis of novel drug entities. The article also highlights the structure activity relationship along with mechanistic insights revealed during the biological evaluation of inhibitors as esterase inhibition. The interactions with the amino acid residues responsible for esterase inhibitory potential of molecules have also been discussed. This compilation will be of great interest for the researchers working in the area of esterase inhibitors. CONCLUSION Rivastigmine derivatives (44-53), tacrine-piperazine hybrid (136), coumarin-benzofuran derivative (169), coumarin-benzylpiperidine hybrid (181) and phenylcinnamide derivative (220) found to be exerting cholinesterase inhibition with IC50 below the range of 1 nM. Whereas, flavone (258) has displayed anticholesterol esterase potential below 1 nM. Benzil like derivative, (273) has also been designed and reported to possess remarkable inhibitory potential (IC50 < 1 nM) against carboxylesterase. These representative results place them in forefront as potential future drug candidates to further develop potent and specific esterase inhibitors.

The exact mechanism of inhibition and adsorption is very essential for designing acid corrosion inhibitors. So far sincere efforts are lacking in explaining the exact mechanism of adsorption and corrosion inhibition for acid corrosion inhibitors. Ammonium oxalate (AO) was investigated as a highly efficient corrosion inhibitor for mild steel in 0.5 M HCl by different theoretical and experimental methods. Experimental methods like gravimetric, impedance, polarization, and metallurgical microscopy were supported by theoretical techniques like DFT, MD simulation, Frontier molecular orbital, and adsorption isotherm studies. Surface studies like the morphology of corroded specimens, nature, and type of corrosion were carried out by metallurgical microscopy technique. Different chemical interaction parameters (global reactivity parameters) between the inhibitor and mild steel provide sufficient information about the adsorption and inhibition mechanism shown by AO for mild steel. A linear correlation regression coefficient was observed between AO concentration and inhibition efficiency. A maximum of 94.94% inhibition efficiency was observed at a 1000 ppm concentration of AO. The polarization study shows that AO act as a mixed inhibitor. Impedance study proves that an increase in AO concentration leads to an increase in charge transfer resistance and hence barrier film thickness. The length of pores, percentage porosity, and intensity of cracks decreases appreciably after the addition of 100 ppm of AO. The biochemical assay of waste acid after gravimetric experiments was observed to be within permissible limits.

A copper-mediated synthesis of diaryl sulfides utilizing Cu(I)-thiophene-2-carboxylate (CuTC) is described. We demonstrate the use of CuTC as a soluble, non-basic catalyst in the coupling of aryl iodides and aryl thiols in the synthesis of synthetically advanced diaryl sulfides. This method allows for the successful coupling of challenging substrates including ortho-substituted and heteroaryl iodides and thiols. Additionally, most of the aryl iodide substrates used here contain the privileged piperazine scaffold bound to a pyrimidine, pyridine, or phenyl ring and thus this method allows for the elaboration of complex piperazine scaffolds into molecules of biological interest. The method described here enables the incorporation of late-stage structural diversity into diaryl sulfides containing the piperazine ring, thus enhancing the number and nature of derivatives available for SAR investigation.

In an attempt to develop potent anti-tubulin agents against most dreadful disease cancer, a library of 28 novel triazole tethered isatin-coumarin hybrids were synthesized by click chemistry approach. Synthesized hybrids were characterized and evaluated against a panel of human cancer cell lines viz. THP-1, COLO-205, HCT-116 and PC-3. Biological assay unveiled that, compounds A-1 to A-6, B-1 to B-4 and C-1 to C-3 displayed significant inhibitory potential against THP-1, COLO-205 and HCT-116 cell lines which were more sensitive towards the designed hybrids. PC-3 among these cell lines was found to be almost resistant. Established SAR revealed marked dependence of the cytotoxic activity on the type of substituent on isatin and the length of carbon-bridge connecting isatin moiety with triazole ring. Unsubstituted isatin and two carbon-bridge were found to be crucial for cytotoxicity. Three most potent hybrids (A-1, A-2 and B-1) were further tested for tubulin polymerization inhibition. Among these three compounds, A-1 found to be endowed with most prominent tubulin polymerization inhibition potential with IC50 value of 1.06µM which was further confirmed by using confocal microscopy. Possible binding interactions between the most potent hybrid molecule A-1 and tubulin were also divulged by molecular modeling studies.

In view of developing effective xanthine oxidase (XO) enzyme inhibitors, a series of 100 pyrano[3,2-d]pyrimidine derivatives was synthesized and evaluated for its in vitro XO enzyme inhibition. Structure activity relationship has also been established. Among all the synthesized compounds, 4d, 8d and 9d were found to be the most potent enzyme inhibitors with IC50 values of 8μM, 8.5μM and 7μM, respectively. Compound 9d was further investigated in enzyme kinetic studies and the Lineweaver-Burk plot revealed that the compound 9d was mixed type inhibitor. Molecular properties of the most potent compounds 4d, 8d and 9d, have also been calculated. Docking study was performed to investigate the recognition pattern between xanthine oxidase and the most potent XO inhibitor, 9d. The study suggests that 9d may block the activity of XO sufficiently enough to prevent the substrate from binding to its active site.

Heterocyclic compounds play a significant role in various biological processes of the human body and many of them are in clinical use due to their diverse, chemical and biological properties. Among these, indole is one of the most promising pharmacologically active molecules. Due to its chemical reactivity, indole has been willingly modified to obtain a variety of new lead molecules, which has been successfully utilized to obtained novel drug candidates for the treatment of different pharmacological diseases. Indole-based compounds such as vincristine (anticancer), reserpine (antihypertensive), amedalin (antidepressant) and many more describe the medicinal and pharmacological importance of the indole in uplifting human life. In this review, we compiled various reports on indole derivatives and their biological significance, including antifungal, antiprotozoal, antiplatelet, anti- Alzheimer’s, anti-Parkinson’s, antioxidant and anticancer potential from 2015 onwards. In addition, structure-activity relationship studies of the different derivatives have been included. We have also discussed novel synthetic strategies developed during this period for the synthesis of different indole derivatives. We believe that this review article will provide comprehensive knowledge about the medicinal importance of indoles and will help in the design and synthesis of novel indole-based molecules with high potency and efficacy.

Hybrid molecules, furnished by combining two or more pharmacophores is an emerging concept in the field of medicinal chemistry and drug discovery that has attracted substantial traction in the past few years. Naturally occurring scaffolds such as coumarins display a wide spectrum of pharmacological activities including anticancer, antibiotic, antidiabetic and others, by acting on multiple targets. In this view, various coumarin-based hybrids possessing diverse medicinal attributes were synthesized in the last five years by conjugating coumarin moiety with other therapeutic pharmacophores. The current review summarizes the recent development (2014 and onwards) of these pharmacologically active coumarin hybrids and demonstrates rationale behind their design, structure-activity relationships (SAR) and mechanistic studies performed on these hybrid molecules. This review will be beneficial for medicinal chemist and chemical biologist, and in general to the drug discovery community and will facilitate the synthesis and development of novel, potent coumarin hybrid molecules serving as lead molecules for the treatment of complex disorders.

Xanthine oxidase (XO) is a versatile molybdoflavoprotein, widely distributed, occurring in milk, kidney, lung, heart, and vascular endothelium. Catalysis by XO to produce uric acid and reactive oxygen species leads to many diseases. Anti hyperuricemic therapy by xanthine oxidase inhibitors has been mainly employed for the treatment of gout. Area covered: This review covers the patent literature (2011-2015) and also presents the interesting strategies/rational approaches employed for the design of xanthine oxidase inhibitors reported recently. Expert opinion: Recent literature indicates that various non purine scaffolds have been extensively investigated for xanthine oxidase inhibition. The significant potential endowed by heteroaryl based compounds, in particularly fused heterocycles clearly highlights their clinical promise and the need for detailed investigation. Studies by various research groups have also revealed that the flavone framework is open for isosteric replacements and structural modifications for yielding potent non purine xanthine oxidase inhibitors. In addition, various plant extracts recently reported to possess significant xanthine oxidase inhibitory potential presents enough promise to initiate a screening program for the identification of other plant extracts and phytoconstituents possessing inhibitory potential towards the enzyme.

Background Topoisomerases are a set of nuclear enzymes that play a vital role in handling of topological consequences of DNA during various genetic activities necessary for vitality of cell. Inhibition of these enzymes consequently leads to the blockage of ligation step of the cell cycle which generates single and double strand breakage in DNA strand. Introduction of these breaks subsequently leads to programmed cell death (Apoptosis). Objective In the past several years, topoisomerases have become one of the most expedient and strategic molecular targets for anticancer drugs and numerous patents have been filed and published on topoisomerase inhibitors. This review compiles the patent literature up to 2016 embracing topo I and II inhibitors as well as dual inhibitors which are structurally adjacent to camptothecin (CPT), natural products such as lamellarins and synthetic trisubstituted pyridines. The present assemblage can be extremely advantageous for the medicinal chemists who are in crave for the development of potential anticancer agents targeting topoisomerases. Conclusion Recent patents indicated that some of the nitrogen containing heteroaromatic compounds have immense potential to inhibit topoisomerase enzyme. In particular, fused N-Heterocycles can be anticipated for their promising therapeutic potential alone or in combination with other anticancer agents. Naphthyridinone and indenoisoquinoline derivatives, described in the preceding sections of this review, are endowed with significant potency against topoisomerase I which clearly indicates the need of preclinical and clinical studies to place them in forefront as potential future drug candidates.

A novel series of triazole tethered coumarin-benzotriazole hybrids based on donepezil skeleton has been designed and synthesized as multifunctional agents for the treatment of Alzheimer’s disease (AD). Among the synthesized compounds 13b showed most potent acetylcholinesterase (AChE) inhibition (IC50 = 0.059 μΜ) with mixed type inhibition scenario. Structure-activity relationship revealed that three-carbon alkyl chain connecting coumarin and triazole is well tolerable for inhibitory potential. Hybrids obtained from 4-hydroxycoumarin and 1-benzotriazole were most potent AChE inhibitors. The inhibitory potential of all compounds against butyrylcholinesterase was also evaluated but all showed negligible activity suggesting that the hybrid molecules are selective AChE inhibitors. 13b (most potent AChE inhibitor) also showed copper-induced Aβ1-42 aggregation inhibition (34.26% at 50 μΜ) and chelating properties for metal ions (Cu2+, Fe2+, and Zn2+) involved in AD pathogenesis along with DNA protective potential against degenerative actions of OH radicals. Molecular modelling studies confirm the potential of 13b in blocking both PAS and CAS of AChE. In addition, interactions of 13b with Aβ1-42 monomer are also streamlined. Therefore, hybrid 13b can act as an effective hit lead molecule for further development of selective AChE inhibitors as multifunctional anti-Alzheimer’s agents.

Protein kinases constitute one of the largest and most functionally diverse gene families that regulate key cell functions. In past several years, kinase inhibition has emerged as potential anti-cancer drug target. Purine is a priveleged heterocyclic nucleus which exists in the chemical architecture of various bioactive compounds. Numerous reports on the use of purine analogues in the treatment of acute leukemias (thiopurines, pentostatin), as antiviral (acyclovir, penciclovir, ganciclovir), as immunosuppressive (azathioprine), as antitumor (vidarabine), as bronchodilator (theophylline) have been revealed. In the past decade, purine analogues have emerged as significantly potent kinase inhibitors. A fair amount of research has been done and several patents have also been published highlighting the kinase inhibitory action of purines. Caffeine, 2-aminopurine, purvalanol-A, seleciclib, FSBA, adenosine thiol analogue possessing purine as the basic moiety fall under this category. In view of the use of purines for the inhibition of kinases, there is need for compilation of data specifying the prominence of purines in the treatment of cancer through this mechanism. The structure of the potent compounds, their IC50 values, models used and the enzymes/ receptors/ targets involved have been presented in this review. The present compilation covers the patents published entailing the purines as kinase inhibitors and the purine drugs employed in chemotherapy.

A series of 4-aryl/heteroaryl-4H-fused pyrans was synthesized via multicomponent reaction in a microwave synthesizer. All the pyrans were evaluated for in vitro xanthine oxidase inhibition. Structure–activity relationship was also established. Among the series of 108 compounds, Compound 5n was the most potent displaying remarkable inhibition against the enzyme with an IC50 value of 0.59 μM. Enzyme kinetic study was carried out for the compound 5n to determine the type of inhibition. The study revealed that the compound 5n was a mixed-type inhibitor. Molecular modelling studies were also performed to figure out the interactions of both the enantiomers of 5n with the amino acid residues of the enzyme.

Bronsted acid catalysts have been used in a number of organic transformations. To overcome limitations, such as toxicity, volatility, high price and hazardous nature of the conventional methods, the catalysts are adsorbed on silica gel to give the benefits and advantages of ready availability, simple work-up procedure, long catalytic life, environment-friendliness, good to excellent yields and recyclability. The uses of such catalysts have gained importance worldwide. This article describes some of the important silicated catalysts, namely, heteropolyacids, polyphosphoric acid, perchloric acid, fluoroboric acid, and silicated sulphuric acid. These catalysts have been used in a number of organic reactions to yield compounds that are important in the chemical and pharmaceutical industries. We summarize the beneficial effects of these catalysts and the reports that have been published on them in the past several years. In the present review, the description of the catalysts are introduced followed by a recent research history, and a comparison between the silica supported catalysts and other (polymer) supported catalysts. The article ends up giving the advantages of these catalytic systems over the conventional catalyst.

The present study involves the design of a series of 3-aryl-9-acetyl-pyridazino[3,4-b]indoles as constrained chalcone analogues. A retrosynthetic route was proposed for the synthesis of target compounds. All the synthesized compounds were evaluated for in-vitro cytotoxicity against THP-1, COLO-205, HCT-116 and A-549 human cancer cell lines. The results indicated that 2a, 3a, 5a and 6a possessed significant cytotoxic potential with an IC50 value ranging from 1.13 to 5.76 μM. Structure activity relationship revealed that the nature of both Ring A and Ring B influences the activity. Substitution of methoxy groups on the phenyl ring (Ring A) and unsubstituted phenyl ring (Ring B) were found to be the preferred structural features. The most potent compound 2a was further tested for tubulin inhibition. Compound 2a was found to significantly inhibit the tubulin polymerization (IC50 value - 2.41 μM against THP-1). Compound 2a also caused disruption of microtubule assembly as evidenced by Immunoflourescence technique. The significant cytotoxicity and tubulin inhibition by 2a was rationalized by molecular modelling studies. The most potent structure was docked at colchicine binding site (PDB ID-1SA0) and was found to be stabilized in the cavity via various hydrophobic and hydrogen bonding interactions.

A Hybrid drug which comprises the incorporation of two drug pharmacophores in one single molecule are basically designed to interact with multiple targets or to amplify its effect through action on another bio target as one single molecule or to counterbalance the known side effects associated with the other hybrid part(.) The present review article offers a detailed account of the design strategies employed for the synthesis of anticancer agents via molecular hybridization techniques. Over the years, the researchers have employed this technique to discover some promising chemical architectures displaying significant anticancer profiles. Molecular hybridization as a tool has been particularly utilized for targeting tubulin protein as exemplified through the number of research papers. The microtubule inhibitors such as taxol, colchicine, chalcones, combretasatin, phenstatins and vinca alkaloids have been utilized as one of the functionality of the hybrids and promising results have been obtained in most of the cases with some of the tubulin based hybrids exhibiting anticancer activity at nanomolar level. Linkage with steroids as biological carrier vector for anticancer drugs and the inclusion of pyrrolo [2,1-c] [1,4]benzodiazepines (PBDs), a family of DNA interactive antitumor antibiotics derived from Streptomyces species in hybrid structure based drug design has also emerged as a potential strategy. Various heteroaryl based hybrids in particular isatin and coumarins have also been designed and reported to posses' remarkable inhibitory potential. Apart from presenting the design strategies, the article also highlights the structure activity relationship along with mechanistic insights revealed during the biological evaluation of the hybrids.

A series of naphthopyrans was synthesized employing silica supported fluoroboric acid under solvent free conditions in a microwave reactor. The catalytic influence of HBF4-SiO2 was investigated in detail to optimize the reaction conditions. The synthesised compounds were evaluated for in vitro xanthine oxidase inhibitory activity for the first time. Structure-activity relationship analyses have also been presented. Among the synthesised compounds, NP-17, NP-19, NP-20, NP-23, NP-24, NP-25 and NP-26 were the active inhibitors with an IC50 ranging from 4 to 17 μM. Compound NP-19 with a thiophenyl ring at position 1 emerged as the most potent xanthine oxidase inhibitor (IC50=4 μM) in comparison to allopurinol (IC50=11.10 μM) and febuxostat (IC50=0.025 μM). The basis of significant inhibition of xanthine oxidase by NP-19 was rationalized by its molecular docking at MTE binding site of xanthine oxidase.

There are various methods available for the development of latent fingerprints on different substrates. This paper presents a new powder method for the development of latent fingerprints on different substrates. In this study, a less expensive, simple and easily available, silica gel G powder (usually used in TLC plates preparation) has been used to develop the latent fingerprints on eight commonly encountered different substrates i.e., plastic, glass, ordinary mirror and metallic substrates, aluminium foil sheet, carbon paper, matchbox, cardboard, glossy-painted wooden substrates, top and writable surface of CD and glazed coloured magazine paper surface. It is observed that it gives very clear results on most of the substrates with clear ridges.

A library of forty 7,8-benzoflavone derivatives was synthesized and evaluated for their inhibitory potential against cholesterol esterase (CEase). Among all the synthesized compounds seven benzoflavone derivatives ( A - 7 , A - 8 , A - 10 , A - 11 , A - 12 , A - 13 , A - 15 ) exhibited significant inhibition against CEase in in vitro enzymatic assay. Compound A - 12 showed the most promising activity with IC 50 value of 0.78 nM against cholesterol esterase. Enzyme kinetic studies carried out for A - 12 , revealed its mixed-type inhibition approach. Molecular protein–ligand docking studies were also performed to figure out the key binding interactions of A - 12 with the amino acid residues of the enzyme’s active site. The A - 12 fits well at the catalytic site and is stabilized by hydrophobic interactions. It completely blocks the catalytic assembly of CEase and prevents it to participate in ester hydrolysis mechanism. The favorable binding conformation of A - 12 suggests its prevailing role as CEase inhibitor.

Kinases control a diverse set of cellular processes comprising of reversible phosphorylation of proteins. Protein kinases play a pivotal role in human tumor cell proliferation, migration and survival of neoplasia. In the recent past, purine based molecules have emerged as significantly potent kinase inhibitors. In view of their promising potential for the inhibition of kinases, this review article focuses on purines which have progressed as kinase inhibitors during the last five years. A detailed account of the design strategies employed for the synthesis of purine analogs exerting inhibitory effects on diverse kinases has been presented. Apart from presenting the design strategies, the article also highlights the structure activity relationship along with mechanistic insights revealed during the biological evaluation of the purine analogs for kinase inhibition. The interactions with the amino acid residues responsible for kinase inhibitory potential of purine based molecules have also been discussed. In this assemblage, purine based protein kinase inhibitors patented in the past have also been summarized in the tabular form. This compilation will be of great interest for the researchers working in the area of protein kinase inhibitors.

Keeping in view the confines allied with presently accessible antitumor agents and success of C5-curcuminoid based bifunctional hybrids as novel antitubulin agnets, molecular hybrids of C5-curcuminoid and coumarin tethered by triazole ring have been synthesized and investigated for in-vitro cytotoxicity against THP-1, COLO-205, HCT-116 and PC-3 human tumor cell lines. The results revealed that the compounds A-2 to A-9, B-2, B-3, B-7 showed significant cytotoxic potential against THP-1, COLO-205 and HCT-116 cell lines, while the PC-3 cell line among these was found to be almost resistant. Structure activity relationship revealed that the nature of Ring X and the length of carbon-bridge (n) connecting triazole ring with coumarin moiety considerably influence the activity. Methoxy substituted phenyl ring as Ring X and two carbon-bridges were found to be the ideal structural features. The most potent compounds (A-2, A-3 and A-7) were further tested for tubulin polymerization inhibition. Compound A-2 was found to significantly inhibit the tubulin polymerization (IC50 = 0.82 μM in THP-1 tumor cells). The significant cytotoxicity and tubulin polymerization inhibition by A-2 was further rationalized by docking studies where it was docked at the curcumin binding site of tubulin.

In view of the drug resistance with most of the currently used anticancer drugs, molecular hybrids of pyrazolyl chalcones and p-nitro benzyl functionalities tethered by triazole ring have been synthesised and evaluated for cytotoxic studies against three human cancer cell lines (THP, COLO-205, A-549). The results of the preliminary investigation exhibited marked dependence of the cytotoxic activity on the electronic factors. Placement of naphthyl (JGPT-11) and trimethoxy phenyl ring (JGPT-6) as ring A proved to be extremely beneficial in enhancing the cytotoxic potential. Thus we herein report the synthesis and cytotoxic studies of a new class of molecular hybrids. Detailed investigation on the biological mechanistic insights of JGPT-11 and 6 is under progress.

In an attempt to develop non-purine-based xanthine oxidase (XO) inhibitors, keeping in view the complications reported with the use of purine-based XO inhibitors, the flavone framework (a class possessing XO inhibitory potential) was used as lead structure for further optimization. By means of structure-based classical bioisosterism, quinolone was used as an isoster for chromone (a bicyclic unit present in flavones), owing to the bioactive potential and drug-like properties of quinolones. This type of replacement does not alter the shape and structural features required for XO inhibition, and also provides some additional interaction sites, without the loss of hydrogen bonding and hydrophobic and arene-arene interactions. In the present study, a series of 2-aryl/heteroaryl-4-quinolones (aza analogs of flavones) was rationally designed, synthesized and evaluated for in vitro XO inhibitory activity. Some notions about structure-activity relationships are presented indicating the influence of the nature of the 2-aryl ring on the inhibitory activity. Important interactions of the most active compound 3l (IC(50) = 6.24 µM) with the amino acid residues of the active site of XO were figured out by molecular modeling.

Natural (−)-(aS, 7S)-colchicine, an alkaloid and toxic natural product is a secondary plant metabolite, obtained from Colchicum autumnale also known as ‘meadow saffron’. Colchicine, among the Indian medicinal plants, is contained in the corms of Colchicum luteum and the seeds of Iphigenia, to the extent of about 0.25 and 0.9 % respectively. These plants are not available in sufficient quantities to warrant any commercial utilization. Natural (−)-colchicine has only one stereogenic centre: carbon-7. The biosynthesis of colchicine involves amino acid precursors, phenylalanine and tyrosine. It is used to treat rheumatic complaints, especially gout, also prescribed for its cathartic and antiemetic effects and also in initial treatment for pericarditis. It is also being investigated for its use as an anti-cancer drug. Colchicine itself is too toxic for human use as an anti-tumour drug and hence its derivatives have been used. Colchicine poisoning has been reported in patients with kidney or liver failure. In neurons, axoplasmic transport is disrupted by colchicine. It is used widely off-label by naturopaths for a number of treatments, including the treatment of back pain and also used as an anti-inflammatory agent for long-term treatment of Behcet’s disease.

Natural products are diverse sources of important chemical constituents. Most of the metabolites isolated from them are heterocycles possessing diverse pharmacological actions. Vasicine, a heterocyclic alkaloid possessing a privileged quinazoline nucleus is primarily present in the leaves o the plant Adhatoda vasica nees, family Acanthaceae. Vasicine and structurally related quinazolines have been an area of interest for the researchers all around the world. The present review provides an up to date compilation of the alkaloid vasicine, its biosynthesis, synthesis, biological attributes, design of its synthetic analogues along with structurally related quinazolines.

Xanthine oxidase inhibitors are currently under scrutiny as attractive therapeutics for disorders such as hyperuricemia, gout, ulcers, cancer, ischemia, hypertension and oxidative damage. The fewer side effects of non-purine xanthine oxidase inhibitors, as compared to purine analogs, make them suitable for further research, which is evidenced by the fact that many articles and patents are now being published on them in the research domain.This review describes the patent literature covering both purine and non-purine analogs as xanthine oxidase inhibitors, up to December 2010, together with their recent highlights in pharmacology. Readers will gain an in-depth knowledge of patents covered and compounds discussed with their therapeutic use.Several of the compounds which are discussed in this article have IC(50) values which offer some advantages over existing molecules such as allopurinol. The available reports on X-ray crystal structures of xanthine oxidase will certainly be beneficial for the design and synthesis of novel xanthine oxidase inhibitors of diverse chemotypes.

Correction for ‘Benzoflavone derivatives as potent antihyperuricemic agents’ by Jatinder V. Singh et al., MedChemCommun, 2019, DOI: 10.1039/c8md00512e.

Background: Microtubules act as a useful and strategic molecular target for various anticancer drugs that binds to its distinct sites in tubulin subunits and inhibits its polymerization and ultimately leads to cell death. Moreover, numerous reports highlight the cytotoxic effects of constraint Combretastatin analogs and thiazolidinone derivatives. Objective: Therefore, the present study investigates the potential of thiazolidinone constraint combretastatin analogs as tubulin inhibitors. Method: By incorporating silica supported fluroboric acid, a series of thiazolidinone constraint combretastatin analogs were synthesized in a microwave reactor under solvent free conditions. To optimize the reaction conditions, the detailed investigation was done for the catalytic influence of HBF4-SiO2. All the synthesized analogs were assessed for in-vitro cytotoxicity against THP-1, COLO-205, HCT-116 and A-549 human cancer cell lines. Top hits were further examined for their tubulin polymerization inhibition and their effect on microtubule assembly. The significant cytotoxicity and tubulin polymerization inhibition of the most potent structure was further rationalized by molecular modelling studies. Results: The results stated that CS-2, CS-3 and CS-20 possessed significant cytotoxic potential with the IC 50 values ranging from 1.21 to 5.50 μM against THP-1, COLO-205, HCT-116 human cancer cell lines. Established structure activity relationship revealed that the nature of Ring A substantially influences the cytotoxic potential of the compounds. Placement of methoxy substituents on the phenyl ring (Ring A) was found to be the most preferred structural feature. Compound CS-2 was found to considerably inhibit the tubulin polymerization (IC 50 value 2.12 μM) and caused disruption of microtubule assembly as demonstrated by immunoflourescence technique. In molecular modelling studies, CS-2 exhibited various hydrophobic as well as hydrogen bonding interactions at colchicine binding site and was found to be stabilized in this cavity. Conclusion: This work provides an efficient methodology for the synthesis of antitubulin thiazolodinonecombretastatin hybrids.

Kinases control a diverse set of cellular processes comprising of reversible phosphorylation of proteins. Protein kinases play a pivotal role in human tumor cell proliferation, migration and survival of neoplasia. In the recent past, purine based molecules have emerged as significantly potent kinase inhibitors. In view of their promising potential for the inhibition of kinases, this review article focuses on purines which have progressed as kinase inhibitors during the last five years. A detailed account of the design strategies employed for the synthesis of purine analogs exerting inhibitory effects on diverse kinases has been presented. Apart from presenting the design strategies, the article also highlights the structure activity relationship along with mechanistic insights revealed during the biological evaluation of the purine analogs for kinase inhibition. The interactions with the amino acid residues responsible for kinase inhibitory potential of purine based molecules have also been discussed. In this assemblage, purine based protein kinase inhibitors patented in the past have also been summarized in the tabular form. This compilation will be of great interest for the researchers working in the area of protein kinase inhibitors.

Keeping in view the limitations associated with currently available anticancer drugs, molecular hybrids of mono carbonyl curcumin and isatin tethered by triazole ring have been synthesized and evaluated for in vitro cytotoxicity against THP-1, COLO-205, HCT-116, A549, HeLa, CAKI-I, PC-3, MiaPaca-2 human cancer cell lines. The results revealed that the compounds SA-1 to SA-9, SB-2, SB-3, SB-4, SB-7 and SC-2 showed a good range of IC50 values against THP-1, COLO-205, HCT-116 and PC-3 cell lines, while the other four cell lines among these were found to be almost resistant. Structure activity relationship revealed that the nature of Ring X and substitution at position R influences the activity. Methoxy substituted phenyl ring as Ring X and H as R were found to be the ideal structural features. The most potent compounds (SA-2, SA-3, SA-4, SA-7) were further tested for tubulin inhibition. Compound SA-2 was found to significantly inhibit the tubulin polymerization (IC50=1.2 μM against HCT-116). Compound SA-2, moreover, lead to the disruption of microtubules as confirmed by immunofluorescence technique. The significant cytotoxicity and tubulin inhibition by SA-2 was streamlined by molecular modeling studies where it was docked at the curcumin binding site of tubulin.

Keeping in view the recent success of molecular hybridization technique in drug design, 2,4-diarylpyrano[3,2-c]chromen-5(4H)-ones as conjugates of coumarins and chalcones have been designed and synthesized in the present study. The catalytic efficiency of various Lewis acids for the synthesis of designed conjugates under neat conditions was investigated, and SiO2 (200–400 mesh)-ZnCl2 was optimized as the best catalyst among the tested ones. The conjugates were evaluated for in-vitro xanthine oxidase activity. The results of the in-vitro assay were quite promising as some conjugates were endowed with remarkable inhibitory potential against the enzyme. HV-8, 11 and 12 were found to be high-potent inhibitors with HV-11 (the most potent inhibitor) possessing an IC50 value of 2.21 µM. The most active conjugate HV-11 was evaluated for the type of inhibition and was found to be a mixed type inhibitor. The compliance of some selected conjugates to the Lipinski rule was also calculated.

A Hybrid drug which comprises the incorporation of two drug pharmacophores in one single molecule are basically designed to interact with multiple targets or to amplify its effect through action on another bio target as one single molecule or to counterbalance the known side effects associated with the other hybrid part(.) The present review article offers a detailed account of the design strategies employed for the synthesis of anticancer agents via molecular hybridization techniques. Over the years, the researchers have employed this technique to discover some promising chemical architectures displaying significant anticancer profiles. Molecular hybridization as a tool has been particularly utilized for targeting tubulin protein as exemplified through the number of research papers. The microtubule inhibitors such as taxol, colchicine, chalcones, combretasatin, phenstatins and vinca alkaloids have been utilized as one of the functionality of the hybrids and promising results have been obtained in most of the cases with some of the tubulin based hybrids exhibiting anticancer activity at nanomolar level. Linkage with steroids as biological carrier vector for anticancer drugs and the inclusion of pyrrolo [2,1-c] [1,4]benzodiazepines (PBDs), a family of DNA interactive antitumor antibiotics derived from Streptomyces species in hybrid structure based drug design has also emerged as a potential strategy. Various heteroaryl based hybrids in particular isatin and coumarins have also been designed and reported to posses' remarkable inhibitory potential. Apart from presenting the design strategies, the article also highlights the structure activity relationship along with mechanistic insights revealed during the biological evaluation of the hybrids.