Design, synthesis, molecular docking, molecular dynamic simulation, and MMGBSA analysis of 7-O-substituted 5-hydroxy flavone derivatives.

A series of chrysin derivatives were designed, synthesized, and evaluated for their antibacterial activity against four different bacterial strains. We have synthesized new propyl-substituted and butyl-substituted chrysin-piperazine derivatives, which show marvellous inhibition against E. coli and S. aureus. The free hydroxyl group at the C-5 position of chrysin improved therapeutic efficacy in vivo and was a beneficial formulation for chemotherapy. All synthesized compounds were confirmed by various spectroscopic techniques such as IR, NMR, HPLC, and mass spectrometry. The compounds exhibited moderate to good inhibition, and their structure-activity relationship (SAR) has also been illustrated. Among the synthesised compounds, compounds 4 and 10 were the most active against S. pyogenes and E. coli, with 12.5 g/mL MICs; additionally, compound 12 exhibits significant activity on both the S. aureus and E. coli stains. Based on the promising activity profile and docking score of compound 12, it was selected for 100 ns MD simulation and post-dynamic binding free energy analysis within the active sites of S. aureus TyrRS (PDB ID: 1JIJ) and E. coli DNA GyrB (PDB ID: 6YD9) to investigate the stability of molecular contacts and to establish how the newly synthesized inhibitors fit together in the most stable conformations.Communicated by Ramaswamy H. Sarma.

Molecular Docking Studies and Biological Evaluation of Berberine-Benzothiazole Derivatives as an Anti-Influenza Agent via Blocking of Neuraminidase.

In this study, we have introduced newly synthesized substituted benzothiazole based berberine derivatives that have been analyzed for their in vitro and in silico biological properties. The activity towards various kinds of influenza virus strains by employing the cytopathic effect (CPE) and sulforhodamine B (SRB) assay. Several berberine-benzothiazole derivatives (BBDs), such as BBD1, BBD3, BBD4, BBD5, BBD7, and BBD11, demonstrated interesting anti-influenza virus activity on influenza A viruses (A/PR/8/34, A/Vic/3/75) and influenza B viral (B/Lee/40, and B/Maryland/1/59) strain, respectively. Furthermore, by testing neuraminidase activity (NA) with the neuraminidase assay kit, it was identified that BBD7 has potent neuraminidase activity. The molecular docking analysis further suggests that the BBD1-BBD14 compounds' antiviral activity may be because of interaction with residues of NA, and the same as in oseltamivir.

Pyrrolo[1,2-a]azepines Coupled with Benzothiazole and Fluorinated Aryl Thiourea Scaffolds as Promising Antioxidant and Anticancer Agents.

BACKGROUND: Cancer remains a major health concern throughout history and is responsible for huge numbers of deaths globally. The sensitivity of cancer cells to anticancer drugs is a crucial factor for developing effective treatments. METHODS: Pyrrolo[1,2-a]azepines coupled with benzothiazole and fluorinated aryl thiourea scaffolds have been synthesized, and their potential as cytotoxic agents was investigated against different cancer cell lines such as human ovarian cancer (SK-OV-3), cervical cancer (HeLa), colon adenocarcinoma (HT-29) and non-small-cell lung carcinoma (A549). Cytotoxicity of new compounds was confirmed using SRB assay against non-cancer MDCK cell line. In addition, free radical scavenging activity of new pyrrolo[1,2-a]azepines was examined by adopting DPPH and ABTS assays. RESULTS: The results concluded that the presence and position of fluorine atom(s) on the thiourea unit played a significant role in order to gain anticipated efficacies. Results of the cytotoxic assay against non-cancer MDCK cells showed that these new derivatives are safe to study further. New structures were confirmed using spectral and elemental analyses. CONCLUSION: Pyrrolo[1,2-a]azepines endowed with a benzothiazole entity and fluorinated aryl thiourea substituents were derived aiming to furnish remarkable antioxidant and anticancer activities. New molecules generated showed interesting biological result correlated with the structure and substituent of the final derivatives. Specifically, numbers and position of fluorine atoms on the thiourea unit influenced the biological profile of the mentioned compounds.

Sulfonylpiperazines based on a flavone as antioxidant and cytotoxic agents.

Chrysin-based sulfonylpiperazines 7a-k were synthesized and investigated for their in vitro free radical scavenging potential as well as cytotoxic efficacies against selected cancer cell lines. Cytotoxicity of the new compounds toward noncancer cells was confirmed using the SRB assay against Madin-Darby Canine Kidney cells. Reaction of piperazine with different substituted benzenesulfonyl chlorides in triethylamine furnished sulfonylpiperazines (3a-k), which were then allowed to react with 7-(4-bromobutoxy)-5-hydroxy-2-phenyl-4H-chromen-4-one (6) prepared reacting chrysin with 1,4-dibromobutane to give the final derivatives 7a-k. The results concluded that chrysin-sulfonylpiperazines exerted better antioxidant and anticancer efficacies than previously studied chrysin-piperazine precursors. For example, compounds 7h, 7j, and 7k with 4-OCF3 , 4-OCH3 , and 2,4-diOCH3 groups exhibited the best antioxidant potential against 2,2-diphenyl-1-picrylhydrazyl (DPPH) and 2,2'-azino-bis-3-ethylbenzothiazoline-6-sulfonic acid (ABTS) radicals. Moreover, halogenated analogues (7b, 7c, 7g, and 7h) demonstrated promising anticancer potential against SK-OV3, HeLa, and HT-29 cell lines, whereas those bearing a methoxy functional group (7j and 7k) had beneficial effects against the cell lines A-549 and HT-29. Thus, it can be confirmed from the bioassay results that the overall structural design as well as proper substitution is crucial to deliver the anticipated biological effects. Spectroscopic techniques such as FT-IR, 1 H NMR, 13 C NMR, mass and elemental analysis (CHN) were carried out to confirm the final structures.

Phenylsulfonyl piperazine bridged [1,3]dioxolo[4,5-g]chromenones as promising antiproliferative and antioxidant agents.

Two series of sulfonylpiperazines linked [1,3]dioxolo[4,5-g]chromenones were synthesized featuring phenyl (7a-k) and chalcone (12a-k) bridge representing flavones or homoisoflavonoids core. New molecules are synthesized utilizing aldol condensation to inspect as antioxidants against DPPH and ABTS+ and antiproliferative agents toward selected human cancer cell lines. Cytotoxicity of new compounds was confirmed using SRB assay against non-cancer MDCK cell line. The results concluded that both individual structures of 7 and 12 were vital for modulating pharmacological potencies and presence of different electron withdrawing and electron donating functional group(s) on the phenylsulfonyl entity yielded varied biological effects. Substituent h (OCF3) and j, k (OCH3) were found to play a crucial role scavenging DPPH and ABTS+ as well as inhibiting cancer cell lines SK-OV-3 and HT-29. Moreover, molecules bearing halogen atom(s) such as substituent b-g expressed excellent inhibitory potential against HeLa and A-549 cancerous cell lines. Bioassay data displayed some interesting structure-activity relationships which are discussed in this paper. The results justified that tested derivatives are promising antioxidants and cytotoxic agents and warrant further structural optimization and bioassay studies. Spectroscopic techniques such as FT-IR, 1H NMR, 13C NMR and elemental analysis (CHN) were carried out to confirm the final structures.

Berberine-piperazine conjugates as potent influenza neuraminidase blocker.

In these studies, we analyzed substituted piperazine based berberine analogs conjugated through a pentyloxy side chain for their in vitro and in silico biological effects. All the final analogs were screened for their in vitro antiviral action against a collection of different influenza virus strains using the CPE assay and SRB assay. Moreover, their cytotoxicity towards non-cancer cell lines was examined employing Madin-Darby canine kidney (MDCK) cell lines. The anti-influenza activities of berberine-piperazine derivatives (BPD) were evaluated in the range from 35.16 µg/mL to 90.25 µg/mL of the IC50s along with cytotoxicity level which was observed in the range 44.8 µg/mL to 3890.6 µg/mL of CC50s towards MDCK cells. In an effort to know the mechanism of action of BPD1-BPD23, results of Neuraminidase inhibition assay and Molecular docking studies carried out against neuraminidase as the target enzyme revealed that titled compounds are potential neuraminidase inhibitors that merge to the active site of neuraminidase, with moderate to high binding energy.

Therapeutic potential of quercetin as a cardiovascular agent.

Flavonoids are integral components of various vegetation and in foods; consequently, they represent an inevitable part of the diet. Historical and epidemiological proof recommend that diet plans consisting of flavonoids such as quercetin have positive health benefits, especially on the heart. Flavonoids have been proven to be active against hypertension, inflammation, diabetes and vascular diseases. Quercetin exhibits significant heart related benefits as inhibition of LDL oxidation, endothelium-independent vasodilator effects, reduction of adhesion molecules and other inflammatory markers, the protective effect on nitric oxide and endothelial function under conditions of oxidative stress, prevention of neuronal oxidative and inflammatory damage and platelet antiaggregant effects. Searching for experimental evidence to validate the cardioprotective effects of quercetin, we review here the recent detailed in vivo studies. Quercetin and its derivatives lead to an enhancement in heart features, indicating the prospective for quercetin to be used therapeutically in the treatment of cardiac diseases. Several evidence-based studies suggest mechanisms to observe cardiovascular diseases such as aging effects, hypertension, angiotensin-converting enzyme activity and endothelial-dependent and independent functions. Different animal models including human are also used to elucidate the in vivo role of quercetin in cardiovascular diseases. The role of quercetin and its derivatives may go beyond their existence in food and has potential as a lead molecule in drug development programs.

A rich source of potential bioactive compounds with anticancer activities by Catharanthus roseus cambium meristematic stem cell cultures.

ETHNOPHARMACOLOGICAL IMPORTANCE: Catharanthus roseus (L.) G. Don. is an important medicinal plant with rich sources of remarkable health benefits consisting more than 100 alkaloids and significant amounts of bioactive compounds, which have been widely used as a folk medicine for treatment of several pathologies. THE AIM OF THE STUDY: In the present study, we isolated and cultured innately undifferentiated cambium meristematic cells (CMCs), which were observed stable cell growth, enhancement of bioactive compounds from C.roseus. MATERIALS AND METHODS: We attempted to determine the effect of association between time-course growth rates, bioactive compounds and terpenoids indole alkaloid (TIA) contents as well as antioxidant and anticancer efficacies of C. roseus CMC suspension culture treated by UV-C. RESULTS: The bioactive compounds, vincristine contents, and antioxidant power were noticed significantly higher in 60 min exposure at 5 cm distances and with the directly collected sample (T7). A similar trend has also been noticed from the anticancer activity. Demonstration of TIA accumulation was found higher at 5 min exposure, at 20 cm distances and 48 h of incubation (T21) and the result of TIA contents had the highest correlation effects of anticancer activities. CONCLUSION: In the current study, we demonstrated that UV-C light could enhance the production of the essential compounds and bioactivities in the CMCs of C. roseus, and thus, C. roseus CMCs have the potential to serve as an industrial platform for the production of bioactive alkaloids and antioxidant, anticancer activity. Moreover, additional efforts should be made to irradiate CMC suspension cultures from C. roseus with UV-C to achieve better pharmacological profiles.

Antioxidant, anti-inflammatory, and enzyme inhibitory activity of natural plant flavonoids and their synthesized derivatives.

The synthesized flavonoid derivatives were examined for their antioxidant, anti-inflammatory, xanthine oxidase (XO), urease inhibitory activity, and cytotoxicity. Except few, all the flavonoids under this study showed significant antioxidant activity (45.6%-85.5%, 32.6%-70.6%, and 24.9%-65.5% inhibition by DPPH, ferric reducing/antioxidant power, and oxygen radical absorption capacity assays) with promising TNF-α inhibitory activity (42%-73% at 10 µM) and IL-6 inhibitory activity (54%-81% at 10 µM) compared with that of control dexamethasone. The flavonoids luteolin, apigenin, diosmetin, chrysin, O3Ꞌ , O7 -dihexyl diosmetin, O4Ꞌ , O7 -dihexyl apigenin, and O7 -hexyl chrysin, showed an inhibition with IC50 values (4.5-8.1 µg/mL), more than allopurinol (8.5 µg/mL) at 5 µM against XO and showing more than 50% inhibition at a final concentration (5 mM) with an IC50 value of ranging from 4.8 to 7.2 (µg/mL) in comparison with the positive control thiourea (5.8 µg/mL) for urease inhibition. Thus, the flavonoid derivatives may be considered as potential antioxidant and antigout agents.

Synthesis and Evaluation of Antioxidant and Cytotoxicity of the N-Mannich Base of Berberine Bearing Benzothiazole Moieties.

BACKGROUND: Berberine, a quaternary ammonium salt from the protoberberine group of benzylisoquinoline alkaloids has drawn high attention for its several biological potencies. OBJECTIVE: To furnish new rationalized derivatives based on berberine core which can deliver promising antioxidant and cytotoxic activities. METHOD: The N-Mannich base of an isoquinoline alkaloid, berberine, bearing substituted benzothiazole moieties was obtained. Novel synthesized analogues were in vitro screened for antioxidant efficacy toward 2,2-diphenyl- 1-picrylhydrazyl (DPPH) and 2,2'-azino-bis(3-ethylbenzothiazoline-6-sulphonic acid) (ABTS) free radicals and in vitro cytotoxicity towards cervical cancer cell lines (HeLa and CaSki), an ovarian cancer cell line (SK-OV-3) and human renal cancer cell line (Caki-2). Cytotoxicity of the compounds toward normal cell lines was examined using the Madin-Darby canine kidney (MDCK) non-cancer cell line. RESULTS: Analogues bearing a methoxy functional group (5e), acid functionality (5c), and a cyano group (5m) showed remarkable radical scavenging potential in DPPH and ABTS bioassays. Potent cytotoxicity exhibited by berberine against the HeLa cell line was attributable to the presence of a 2-aminobenzothaizole moiety (5a) and its 6-chloro congener (5g) on the berberine core, and the 6-cyano group (5m) on the benzothiazole ring revealed strong sensitivity for the CaSki cell line, whereas subjected scaffolds demonstrated diminished activity against the SK-OV-3 cell line. In addition, the compound with a 2-aminobenzothaizole moiety (5a), compound with methoxy functional group (5e) and compound with cyano group appeared with the most significant cytotoxicity effect in Caki-2 cell line. Their structures have been elucidated by FT-IR, 1H NMR, 13C NMR, and elemental analyses (CHN) essential research. CONCLUSION: N-Mannich bases of berberine were efficiently generated utilizing pharmacologically diverse substituted 2-aminobenzothiazole entities and final compounds were found remarkably active in antioxidant and cytotoxic assay. Hence, such types of compounds can be further studied or rationalized in future drug discovery studies.

ß-Alanine intercede metabolic recovery for amelioration of human cervical and renal tumors.

ß-Alanine is a non-essential amino acid and presents as a major component of various sports supplements. It is a non-proteogenic amino acid, formed in vivo by degradation of carnosine, anserine, balenine, and dihydrouracil. The present study was aimed at investigating the anti-tumor effects of ß-alanine in renal and cervical tumor cells. Sulforhodamine-B assay and flow cytometric analysis were used to measure cell viability. Lactate dehydrogenase (LDH) expression was analyzed using FITC-conjugated fluorescent antibody. The cellular adenosine triphosphate (ATP) content was measured using bioluminescence method. Cell migration was determined by the simple standard-scratch method. ß-Alanine reduced renal and cervical cell growth significantly. Percentage of inhibition of renal and cervical tumor cells was increased at higher concentration of ß-alanine. LDH expression and ATP content were significantly reduced in renal and cervical tumor cells in a dose-dependent manner. Renal and cervical tumor cell migration were significantly reduced following 10 and 100 mM of ß-alanine treatment. In our study, ß-alanine exerts no significant effect on normal MDCK cells except a marginal effect at the highest concentration (100 mM). In summary, our experimental data suggest that ß-alanine may be a potential anti-tumor agent exhibiting several anti-cancer effects in renal and cervical tumor cells.

Synthesis of N-Mannich bases of berberine linking piperazine moieties revealing anticancer and antioxidant effects.

A new Mannich base series of piperazine linked berberine analogues was furnished in this study to screen the antioxidant and anticancer potential of the resultant analogues. Alkoxy group at a C-9 position of berberine was converted to hydroxyl functionality to enhance the ability of final scaffolds binding to the target of drug action mainly through hydrophobic effect, conjugation effect, whereas Mannich base functionality was introduced on the C-12 position of berberine. Scaffolds were investigated for their free radical scavenging antioxidant potential in FRAP and DPPH assay, whereas tested to check their Fe+3 reducing power in ABTS assay. The radical scavenging potential of the final derivatives 4a-j was found excellent with IC50s, <13 µg/mL and < 8 µg/mL in DPPH and ABTS assay, respectively, whereas some analogues showed significant Fe+3 reducing power with absorption at around 2 nm in the FRAP assay. Anticancer effects of titled compounds were inspected against cervical cancer cell line Hela and Caski adapting SRB assay, in which analogues 4a-j presented <6 µg/mL of IC50s, and >30 of therapeutic indices, thus exerting low cytotoxic values against Malin-Darby canine kidney (MDCK) cell lines at CC50s >125 µg/mL. Hence, from the bioassay outcomes it can be stated that these analogues are dual active agents as the scavengers of reactive oxygen species and inhibitors of the cancerous cells as compounds with halogen functional group have overall good pharmacological potential in assays studied in this research. Correct structure of the final compounds was adequately confirmed on the basis of FT-IR and 1H NMR as well as elemental analyses.

Kinase Inhibitor Indole Derivatives as Anticancer Agents: A Patent Review.

Cancer accounts for a number of deaths each year. Consequently, prevention of this deadly disease is more challenging and hence the invention of new anticancer agents is of utmost importance. The current review elaborates the importance of indole designs as patented in the form of anticancer druglike molecules targeting different cites of biological arena. Specific attention was given to kinases such as platelet-derived growth factor receptor, vascular endothelial growth factor receptor and fibroblast growth factor receptor, Bruton's tyrosine kinase, anaplastic lymphoma kinase, Janus kinase, cyclin-dependent kinase aurora kinases A, B and C, checkpoint kinases, protein kinase R, Pim kinases, phosphoinositide 3- kinase, altered proteins kinases, polo-like kinase and many more. Moreover, the article summarizes the mode of action through the particular functions of kinases and the inhibitory potential of indole derivatives toward specific kinase. Certain patents gathered in the existing review article suggest that indole core can be a versatile foundation to discover drug-like kinase inhibitor molecules and modification of substituents existing on the indole moiety may have important impact on the pharmacokinetic and pharmacodynamics aspects of the resultant scaffolds. The information presented here would gather a great deal of interest to identify the new molecular designs bearing indole nucleus presenting novel anticancer drugs with a wide variety of biological targets involved in cancer pathology focusing on the inhibition of tyrosine kinases, serine/threonine-specific protein kinases, cyclin-dependent kinases, lipid kinases and altered protein kinases.

Visible upconversion in Er3+/Yb3+ co-doped LaAlO3 phosphors.

The Er3+ doped and Er3+/Yb3+ co-doped LaAlO3 phosphors have been synthesized by the combustion method and characterized their structural, morphological, elemental, vibrational and optical properties. The optical absorption and upconversion properties of the synthesized phosphors have been studied. Upon co-doping Yb3+ ions into Er3+:LaAlO3, the blue, green and red upconversion emissions of Er3+ ions have been enhanced about ~20, ~54 and ~22 times, under 978nm laser excitation. The observed upconversion emissions could be due to excited state absorption in Er3+:LaAlO3, whereas energy transfer is dominant mechanism in Er3+/Yb3+:LaAlO3 phosphors. The tuning in the color emitted from the synthesized phosphors towards the green region has been found due to incorporation of the Yb3+ ions. With increase in the pump power, the color emitted from the co-doped phosphor is not tuned significantly, showing its applicability in making the green display devices.

Piperazine derivatives for therapeutic use: a patent review (2010-present).

INTRODUCTION: Piperazine, a six membered nitrogen containing heterocycle, is of great significance to the rational design of drugs. This moiety can be found in a plethora of well-known drugs with various therapeutic uses, such as antipsychotic, antihistamine, antianginal, antidepressant, anticancer, antiviral, cardio protectors, anti-inflammatory, and imaging agents. Slight modification to the substitution pattern on the piperazine nucleus facilitates a recognizable difference in the medicinal potential of the resultant molecules. AREAS COVERED: Scifinder was the main source used to search for patents containing piperazine compounds with therapeutic uses. The article describes a variety of molecular designs bearing piperazine entity furnishing CNS agents, anticancer, cardio-protective agents, antiviral, anti-tuberculosis, anti-inflammatory, antidiabetic, and antihistamine profiles, as well as agents relieving pain and useful in imaging applications. EXPERT OPINION: The great interest gathered to explore piperazine based molecules in relatively few years reflects the broad potential of the entity. Earlier, this scaffold was considered to express CNS activity only. However, a significant increase in research covering studies of several different activities of piperazine ring suggest a successful emergence of the pharmacophore. Certain patents outlined in the present article recommend that piperazines can be a flexible building block to discover drug-like elements and modification of substituents present on the piperazine ring may have a significant impact on the pharmacokinetic and pharmacodynamics factors of the resulting molecules. This article aims to provide insights to piperazine based molecular fragments that would assist drug discoverers to rationally design molecules for various diseases. We anticipate, and highly recommend, further therapeutic investigations on this motif.

Chrysin-piperazine conjugates as antioxidant and anticancer agents.

Synthesis of 7-(4-bromobutoxy)-5-hydroxy-2-phenyl-4H-chromen-4-one intermediate treating chrysin with 1,4-dibromobutane facilitated combination of chrysin with a wide range of piperazine moieties which were equipped via reacting the corresponding amines with bis(2-chloroethyl)amine hydrochloride in diethylene glycol monomethyl ether solvent. Free radical scavenging potential of prepared products was analyzed in vitro adopting DPPH and ABTS bioassay in addition to the evaluation of in vitro anticancer efficacies against cervical cancer cell lines (HeLa and CaSki) and an ovarian cancer cell line SK-OV-3 using SRB assay. Bearable toxicity of 7a-w was examined employing Madin-Darby canine kidney (MDCK) cell line. In addition, cytotoxic nature of the presented compounds was inspected utilizing Human bone marrow derived mesenchymal stem cells (hBM-MSCs). Overall, 7a-w indicated remarkable antioxidant power in scavenging DPPH(·) and ABTS(·+), particularly analogs 7f, 7j, 7k, 7l, 7n, 7q, 7v, 7w have shown promising free radical scavenging activity. Analogs 7j and 7o are identified to be highly active candidates against HeLa and CaSki cell lines, whereas 7h and 7l along with 7j proved to be very sensitive towards ovarian cancer cell line SKOV-3. None of the newly prepared scaffolds showed cytotoxic nature toward hBM-MSCs cells. From the structure-activity point of view, nature and position of the electron withdrawing and electron donating functional groups on the piperazine core may contribute to the anticipated antioxidant and anticancer action. Different spectroscopic techniques (FT-IR, (1)H NMR, (13)C NMR, Mass) and elemental analysis (CHN) were utilized to confirm the desired structure of final compounds.

Synthesis of 9-O-3-(1-piperazinyl/morpholinyl/piperidinyl)pentyl-berberines as Potential Antioxidant and Cytotoxic Agents.

A new series of 9-O-3-(1-piperazinyl/morpholinyl/piperidinyl)pentyl-berberines has been efficiently formulated via coupling 1,5-dibromopentane with berberrubine which was obtained by treating berberine in a vacuum oven at optimum temperature and pressure. Nucleophilic substitution of a variety of substituted piperazines, morpholine, carbazole and piperidine furnished analogues 5a-i. Final compounds were evaluated for their in vitro antioxidant activity using 2,2-diphenyl-1-picrylhydrazyl (DPPH) and 2,2'-azino-bis(3-ethylbenzothiazoline-6- sulphonic acid) (ABTS) bioassays. Also, cancer cell inhibitory potential of titled compounds was screened for cervical cancer, HeLa and CaSki employing SRB assay in terms of cytotoxicity. A minimum inhibitory concentration of 5a-i towards normal cells was studied using Madin-Darby canine kidney (MDCK) cell line. Final compounds with carbazole and 1-(naphthalen-2-yl)piperazine showed excellent free radical scavenging efficacies in DPPH and ABTS bioassays, respectively. The presence of naphthyl, benzhydryl, benzoyl, furoyl and heterocyclic rings on the piperazine system was essential to exert anticipated cytotoxic effects against cancer cell lines. The structure of the final compounds was adequately confirmed via spectroscopic techniques, elemental analysis analysis and characterization of physical properties.

Chrysin-benzothiazole conjugates as antioxidant and anticancer agents.

7-(4-Bromobutoxy)-5-hydroxy-2-phenyl-4H-chromen-4-one, obtained from chrysin with 1,4-dibromobutane, was combined with a wide range of 6-substituted 2-aminobenzthiazoles, which had been prepared from the corresponding anilines with potassium thiocyanate. Free radical scavenging efficacies of newer analogues were measured using DPPH and ABTS assays, in addition to the assessment of their anticancer activity against cervical cancer cell lines (HeLa and CaSki) and ovarian cancer cell line (SK-OV-3) implementing the SRB assay. Cytotoxicity of titled compounds was checked using Madin-Darby canine kidney (MDCK) non-cancer cell line. Overall, 6a-r indicated remarkable antioxidant power as DPPH and ABTS(+) scavengers; particularly the presence of halogen(s) (6g, 6h, 6j-6l) was favourable with IC50 values comparable to the control ascorbic acid. Unsubstituted benzothiazole ring favored the activity of resultant compounds (6a and 6r) against HeLa cell line, whereas presence of chlorine (6g) or a di-fluoro group (6k) was a key to exert strong action against CaSki. Moreover, a mono-fluoro (6j) and a ketonic functionality (6o) were beneficial to display anticipated anticancer effects against ovarian cancer cell line SK-OV-3. The structural assignments of the new products were done on the basis of IR, (1)H NMR, (13)C NMR spectroscopy and elemental analysis.

Nitroimidazoles, Quinolones and Oxazolidinones as Fluorine Bearing Antitubercular Clinical Candidates.

Tuberculosis is a leading killer of lives worldwide and the global curse of multi-drug resistant tuberculosis is attaining really dangerous levels. Synergistic interaction of HIV and TB is the twin epidemics in resource-limited countries as each potentiate progression of the other. The increasing emergence of MDR-TB and XDR-TB place an immense burden for the treatment of TB with currently available drugs. The situation urgently demands for the discovery of new drugs with novel mode of action and differs in structural features in order to overcome resistance appears in conventional TB therapeutics. The present report covers the discovery of three classes of antituberculosis drugs, Nitroimidazoles, Quinolones and Oxazolidinones, undergoing clinical development with fluorine atom in their structures. Highly electronegative fluorine atom plays a signature role in advancing medicinal innovations as it existence in the drug compounds critically influences metabolic stability and lipophilicity thereby delaying its elimination by the body which results into a long term in vivo efficiency of the drug. Presence of fluorine atom(s) in the drug structures described in this report, has been associated with the several fold increase in the overall potency of the compound as demonstrated since the early discoveries. 6 Fluorinated derivatives from these three classes as pretomanid, delamanid, moxifloxacin, gatifloxacin, linezolid and sutezolid have been discussed with their antituberculosis effects, mode of action, chemical synthetic routes and results of clinical studies.

Pyrroloaryls and pyrroloheteroaryls: Inhibitors of the HIV fusion/attachment, reverse transcriptase and integrase.

Heterocyclic compounds execute a very important role in drug design and discovery. This article provides the basic milestones of the research for pyrroloaryl and pyrroloheteroaryl based components targeting HIV viral replication cycle. Anti-HIV activity is elaborated for several classes of pyrrolo-compounds as pyrrolopyridines, pyrrolopyrimidines, pyrrolopyridazines, pyrrolobenzodiazepinones, pyrrolobenzothiazepines, pyrrolobenzoxazepinones, pyrrolophenanthridines, pyrroloquinoxalines, pyrrolotriazines, pyrroloquinolines, pyrrolopyrazinones, pyrrolothiatriazines, arylthiopyrroles and pyrrolopyrazolones targeting two essential HIV enzymes, reverse transcriptase and integrase as well as attachment/fusion of HIV virons to the host CD-4 cell. Such attempts were resulted in a discovery of highly potent anti-HIV agents suitable for clinical trials, for example, BMS-378806, BMS-585248, BMS-626529, BMS-663068, BMS-488043 and BMS-663749, etc. as anti-HIV attachment agents, triciribine, QX432, BI-1 and BI-2 as HIV RT inhibitors which are in preclinical or clinical development. Mechanism of action of compounds presented in this article towards the suppression of HIV attachment/fusion as well as against the activities of HIV enzymes reverse transcriptase and integrase has been discussed. Relationships of new compounds' molecular framework and HIV viral target has been overviewed in order to facilitate further construction of promising anti-HIV agents in future drug discovery process.