02427nas a2200301 4500008004100000022001400041245009900055210006900154260006700223300001200290490000700302520136400309653002801673653003301701653001601734653002701750100002101777700002101798700002301819700003401842700001801876700001901894700002201913700002201935700002101957700002401978856012302002 2015 eng d a1747-027700aTargeting dormant tuberculosis bacilli: results for molecules with a novel pyrimidone scaffold0 aTargeting dormant tuberculosis bacilli results for molecules wit a111 RIVER ST, HOBOKEN 07030-5774, NJ USAbWILEY-BLACKWELLcFEB a201-2070 v853 a

Our inability to completely control TB has been due in part to the presence of dormant mycobacteria. This also renders drug regimens ineffective and is the prime cause of the appearance of drug-resistant strains. In continuation of our efforts to develop novel antitubercular agents that especially target dormant mycobacteria, a set of 55 new compounds belonging to the pyrimidone class were designed on the basis of CoMFA and CoMSIA studies, and these were synthesized and subsequently tested against both the dormant and virulent BCG strain of M.tuberculosis. Some novel compounds have been identified which selectively inhibit the dormant tuberculosis bacilli with significantly low IC50 values. This study reports the second molecule after TMC-207, having the ability to inhibit tuberculosis bacilli exclusively in its dormant phase. The synthesis was accomplished by a modified multicomponent Biginelli reaction. A classification model was generated using the binary QSAR approach - recursive partitioning (RP) to identify structural characteristics related to the activity. Physicochemical, structural, topological, connectivity indices, and E-state key descriptors were used for generation of the decision tree. The decision tree could provide insights into structure-activity relationships that will guide the design of more potent inhibitors.

10aAntitubercular activity10adormant tuberculosis bacilli10apyrimidones10arecursive partitioning1 aJoshi, Rohit, R.1 aBarchha, Avinash1 aKhedkar, Vijay, M.1 aPissurlenkar, Raghuvir, R. S.1 aSarkar, Sampa1 aSarkar, Dhiman1 aJoshi, Rohini, R.1 aJoshi, Ramesh, A.1 aShah, Anamik, K.1 aCoutinho, Evans, C. uhttp://library.ncl.res.in/content/targeting-dormant-tuberculosis-bacilli-results-molecules-novel-pyrimidone-scaffold-002320nas a2200313 4500008004100000022001400041245010700055210006900162260010600231300001400337490000700351520123800358653000601596653000601602653001701608653002801625653001701653653002201670653001301692653001301705100002501718700002701743700002401770700002301794700002301817700001901840700002101859856012601880 2016 eng d a0960-894X00aSynthesis and antitubercular activity of new 1,3,4-oxadiazoles bearing pyridyl and thiazolyl scaffolds0 aSynthesis and antitubercular activity of new 134oxadiazoles bear aTHE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, ENGLANDbPERGAMON-ELSEVIER SCIENCE LTDcAUG a3646-36510 v263 a

In search of more potent and safe new antitubercular agents, here new 2-pyridinyl substituted thiazolyl-5-aryl-1,3,4-oxadiazoles (6a-o), have been designed and synthesized using thionicotinamide as a starting, following novel multistep synthetic route. An intermediate, pyridinyl substituted thiazolyl acid hydrazide (4) when condensed with benzoic acids/nicotinic acids (5a-o) in the presence of silica supported POCl3 yielded better to excellent yields of the title compounds. All the synthesized compounds (6a-o) and intermediate acid hydrazide (4) have been screened for their in vitro antitubercular activity against Mycobacterium tuberculosis H37Ra (MTB) and Mycobacterium bovis BCG. Amongst them, 6f, 6j, 6l and 6o have revealed promising activity against M. bovis BCG at concentrations less than 3 mu g/mL. These compounds have shown low cytotoxicity (CC50: > 100 mu g/mL) towards four human cancer cell lines. Molecular docking study has also been performed against mycobacterial enoyl reductase (InhA) enzyme to gain an insight into the binding modes of these molecules and recorded good binding affinity. The ADME properties the title products have also been analyzed. (C) 2016 Elsevier Ltd. All rights reserved.

10a110a310a4-Oxadiazole10aAntitubercular activity10aCytotoxicity10aMolecular docking10aPyridine10aThiazole1 aDhumal, Sambhaji, T.1 aDeshmukh, Amarsinh, R.1 aBhosle, Manisha, R.1 aKhedkar, Vijay, M.1 aNawale, Laxman, U.1 aSarkar, Dhiman1 aMane, Ramrao, A. uhttp://library.ncl.res.in/content/synthesis-and-antitubercular-activity-new-134-oxadiazoles-bearing-pyridyl-and-thiazolyl02542nas a2200325 4500008004100000022001400041245016900055210006900224260010700293300001400400490000700414520138800421653000601809653000601815653001701821653002801838653001701866653001101883653002201894653001301916100001801929700001901947700001801966700001901984700001902003700002302022700002102045700001902066856013102085 2016 eng d a0960-894X00aSynthesis, biological evaluation and molecular docking study of some novel indole and pyridine based 1,3,4-oxadiazole derivatives as potential antitubercular agents0 aSynthesis biological evaluation and molecular docking study of s aTHE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, ENGLANDbPERGAMON-ELSEVIER SCIENCE LTDcAPR  a1776-17830 v263 a

A series of indole and pyridine based 1,3,4-oxadiazole derivatives 5a-t were synthesized and evaluated for their in vitro antitubercular activity against Mycobacterium tuberculosis H37Ra (MTB) and Mycobacterium bovis BCG both in active and dormant state. Compounds 5b, 5e, 5g and 5q exhibited very good antitubercular activity. All the newly synthesized compounds 5a-t were further evaluated for antiproliferative activity against HeLa, A549 and PANC-1 cell lines using modified MTT assay and found to be noncytotoxic. On the basis of cytotoxicity and MIC values against Mycobacterium bovis BCG, selectivity index (SI) of most active compounds 5b, 5e, 5g and 5q was calculated (SI = GI(50)/MIC) in active and dormant state. Compounds 5b, 5e and 5g demonstrated SI values >= 10 against all three cell lines and were found to safe for advance screening. Compounds 5a-t were further screened for their antibacterial activity against four bacteria strains to assess their selectivity towards MTB. In addition, the molecular docking studies revealed the binding modes of these compounds in active site of enoyl reductase (InhA), which in turn helped to establish a structural basis of inhibition of mycobacteria. The potency, low cytotoxicity and selectivity of these compounds make them valid lead compounds for further optimization. (C) 2016 Elsevier Ltd. All rights reserved.

10a110a310a4-Oxadiazole10aAntitubercular activity10aCytotoxicity10aIndole10aMolecular docking10aPyridine1 aDesai, N., C.1 aSomani, Hardik1 aTrivedi, Amit1 aBhatt, Kandarp1 aNawale, Laxman1 aKhedkar, Vijay, M.1 aJha, Prakash, C.1 aSarkar, Dhiman uhttp://library.ncl.res.in/content/synthesis-biological-evaluation-and-molecular-docking-study-some-novel-indole-and-pyridine-002854nas a2200337 4500008004100000022001400041245014000055210006900195260000800264300001200272490000700284520166800291653002401959653002801983653003502011653002202046653004102068653002302109100002302132700002202155700003002177700002702207700002302234700002202257700002102279700002602300700002002326700002002346700001902366856013102385 2019 eng d a1573-409900aNon nucleoside reverse transcriptase inhibitors, molecular docking studies and antitubercular activity of thiazolidin-4-one derivatives0 aNon nucleoside reverse transcriptase inhibitors molecular dockin cJAN a433-4440 v153 a

Background: Management of Co-existence of Acquired immunodeficiency syndrome and Tuberculosis has become a global challenge due to the emergence of resistant strains and pill burden. Objective: Hence the aim of the present work was to design and evaluate compounds for their dual activity on HIV-1 and Tuberculosis (TB). Methods: A series of seven, novel Thiazolidin-4-one derivatives were synthesized and evaluated for their anti-HIV and anti-tubercular activity along with Molecular docking studies. All the seven compounds displayed promising activity against the replication of HIV-1 in cell-based assays. The four most active compounds were further evaluated against X4 tropic HIV-1(UG)(070) and R5 tropic HIV-1(vB59) primary isolates. The binding affinity of all the designed compounds for HIV-RT and Mycobacterium tuberculosis Enol Reductase (MTB InhA) was gauged by molecular docking studies which revealed crucial thermodynamic interactions governing their binding. Results: The CC50 values for the test compounds were in the range of, 15.08-34.9 mu g/ml, while the IC50 values were in the range of 16.1-27.13(UG(070); X4) and 12.03-23.64 (VB59; R5) mu g/ml. The control drug Nevirapine (NVP) exhibited CC50 value of 77.13 mu g/ml and IC50 value of 0.03 mu g/ml. Amongst all these compounds, compound number 3 showed significant activity with a TI value of 2.167 and 2.678 against the HIV-1 X4 and the R5 tropic virus respectively. In anti-mycobacterial screening, the compounds proved effective in inhibiting the growth of both log phase and starved MTB cultures. Conclusion: Compound 3 has been found to be active against HIV-1 as well as MTB.

10aanti-HIV-1 activity10aAntitubercular activity10ahuman immunodeficiency virus-110aMolecular docking10aNon nucleoside reverse transcriptase10athiazolidin-4-ones1 aChitre, Trupti, S.1 aPatil, Shital, M.1 aSujalegaonkar, Anagha, G.1 aAsgaonkar, Kalyani, D.1 aKhedkar, Vijay, M.1 aGarud, Dinesh, R.1 aJha, Prakash, C.1 aGaikwad, Sharddha, Y.1 aKulkarni, Smita1 aChoudhari, Amit1 aSarkar, Dhiman uhttp://library.ncl.res.in/content/non-nucleoside-reverse-transcriptase-inhibitors-molecular-docking-studies-and-antitubercular02358nas a2200241 4500008004100000022001400041245012700055210006900182260000800251300001200259490000700271520148100278653002801759653004101787653002201828100002401850700001901874700002901893700002101922700002301943700001901966856013101985 2022 eng d a0272-439100aConventional and microwave-assisted organic synthesis of novel antimycobacterial agents bearing furan and pyridine hybrids0 aConventional and microwaveassisted organic synthesis of novel an cAPR a416-4310 v833 a

Drug resistance in tuberculosis poses a serious threat to humanity because currently available antitubercular drugs are ineffective against Mycobacterium tuberculosis (M. tuberculosis). As a result, the approval of Bedaquiline and Delamanid for the treatment of drug-resistant tuberculosis was accelerated. Still, there is an urgent need to search for new antitubercular drugs with novel mechanisms of action (MoA). Due to this, we have designed a synthetic strategy by utilizing microwave-assisted organic synthesis. We have compared our method with the conventional procedure, and the data show that our procedure is more effective in the preparation of title compounds. A unique series of 1-(2-(furan-2-yl)-5-(pyridin-4-yl)-1,3,4-oxadiazol-3(2H)-yl)-3-(aryl)-pr op-2-en-1-ones (5a-o) was synthesized utilizing conventional and microwave-assisted techniques. Synthetic compounds were investigated for antitubercular activity against Mycobacterium TB H37Ra and Mycobacterium bovis (M. bovis). Compound 5b was reported to be the most effective against M. tuberculosis H37Ra (97.69 percent inhibition at 30 mu g/ml) and M. bovis (97.09 percent inhibition at 30 mu g/ml). An in silico binding affinity study of mycobacterial enoyl-acyl carrier protein reductase (InhA) reveals the binding mechanism and thermodynamic interactions that determine these molecule's binding affinity. Compound 5b had a high glide score of -8.991 and low glide energy of -49.893 kcal/mol.

10aAntitubercular activity10amicrowave-assisted organic synthesis10aMolecular docking1 aDesai, Nisheeth, C.1 aBhatt, Kandarp1 aJadeja, Dharmpalsinh, J.1 aMehta, Harsh, K.1 aKhedkar, Vijay, M.1 aSarkar, Dhiman uhttp://library.ncl.res.in/content/conventional-and-microwave-assisted-organic-synthesis-novel-antimycobacterial-agents-bearing01904nas a2200265 4500008004100000022001400041245014800055210006900203260000800272300001400280490000700294520096200301653002801263653001301291653001701304653001701321653002901338100003001367700002401397700002401421700001901445700002301464700002601487856012501513 2022 eng d a1040-663800a[DBUH][OAc]-catalyzed domino synthesis of novel benzimidazole incorporated 3,5-Bis (Arylidene)-4-piperidones as potential antitubercular agents0 aDBUHOAccatalyzed domino synthesis of novel benzimidazole incorpo cNOV a7010-70240 v423 a

A series of new benzimidazole incorporated 3,5-bis (arylidene)-4-piperidones were synthesized by using aryl aldehydes, piperidinone, 2-(chloromethyl)-benzimidazole and DBU acetate [DBUH][OAc] act as a catalyst under solvent free condition in excellent yields. The synthesized compounds were screened for their in vitro antimycobacterial activity against M. tuberculosis H37Ra (MTB) and M. bovis BCG strains. The compounds 4a, 4b, 4e, 4i, 4k and 4l are highly potent against both the strains. Most of the active compounds are non-cytotoxic against MCF-7, A549, HCT 116 and THP-1 cell lines. Furthermore, a molecular docking study of these compounds was carried out to investigate their binding pattern with the target, active site of mycobacterial enoyl-acyl carrier protein reductase (Inh A). Therefore, these compounds can be subjected for further optimization and drug development which could give promising chemical leads for treatment of TB.

10aAntitubercular activity10acurcumin10aCytotoxicity10aIonic liquid10amulticomponent reactions1 aSubhedar, Dnyaneshwar, D.1 aShaikh, Mubarak, H.1 aNagargoje, Amol, A.1 aSarkar, Dhiman1 aKhedkar, Vijay, M.1 aShingate, Bapurao, B. uhttp://library.ncl.res.in/content/dbuhoac-catalyzed-domino-synthesis-novel-benzimidazole-incorporated-35-bis-arylidene-4