01012nas a2200181 4500008004100000022001400041245004300055210004300098260007100141300001400212490000700226520043300233100002400666700001900690700002500709700002100734856007500755 2013 eng d a1523-706000aFirst total synthesis of hunanamycin A0 aFirst total synthesis of hunanamycin A a1155 16TH ST, NW, WASHINGTON, DC 20036 USAbAMER CHEMICAL SOCcSEP a4556-45590 v153 a

The first total synthesis of hunanamycin A, an antibiotic natural product with a pyrido[1,2,3-de]quinoxaline-2,3-dione core from a marine-derived Bacillus hunanensis, is disclosed. The present effort provides access to sufficient amounts of scarce hunanamycin A for further biological evaluation and confirmation of the assigned absolute configuration. In addition, four new analogues of the natural product are reported.

1 aShingare, Rahul, D.1 aVelayudham, R.1 aGawade, Jalindar, R.1 aReddy, Srinivasa uhttps://library.ncl.res.in/content/first-total-synthesis-hunanamycin-001340nas a2200253 4500008004100000022001400041245013000055210006900185260007700254300001400331520038900345653001700734653001300751653002600764653001400790653002200804100002500826700001700851700002400868700002100892700002400913700002100937856012800958 2014 eng d a1434-193X00aGeneral approach to N-heterocyclic carbenes with a fused tetracyclic core: ligands for suzuki-miyaura cross-coupling reaction0 aGeneral approach to Nheterocyclic carbenes with a fused tetracyc aBOSCHSTRASSE 12, D-69469 WEINHEIM, GERMANYbWILEY-V C H VERLAG GMBHcJUL a4482-44863 a

The synthesis of an N-heterocyclic carbene (NHC) based on a tetracyclic scaffold by using simple, general, and scalable chemistry is disclosed. The developed route is suitable for introducing multiple substitutions on the tetracyclic scaffold. The utility of the present NHC as a ligand in the Suzuki-Miyaura cross-coupling reaction is demonstrated with a low catalyst loading.

10aC-C coupling10acarbenes10aHomogeneous catalysis10aN ligands10asynthetic methods1 aSutar, Revannath, L.1 aKumar, Vinod1 aShingare, Rahul, D.1 aThorat, Shridhar1 aGonnade, Rajesh, G.1 aReddy, Srinivasa uhttps://library.ncl.res.in/content/general-approach-n-heterocyclic-carbenes-fused-tetracyclic-core-ligands-suzuki-miyaura-001445nas a2200229 4500008004100000022001400041245010200055210006900157260010600226300001400332490000700346520057400353653001800927653002500945653002500970653002000995653001501015100002401030700002101054700002101075856011901096 2016 eng d a0040-403900aMulti-gram scale synthesis of hunanamycin A, an antibiotic natural product from the marine source0 aMultigram scale synthesis of hunanamycin A an antibiotic natural aTHE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, ENGLANDbPERGAMON-ELSEVIER SCIENCE LTDcAUG a3662-36630 v573 a

A simple, practical, and biomimetic approach to access antibiotic natural product hunanamycin A starting from readily available inexpensive material Riboflavin is disclosed here. The present synthesis consists of three operationally simple, protecting group free steps and it is far superior when compared with the previous route. Using this route one can make multi-gram quantities of the natural product which will help in further biological assays, in particular exploring the potential of treating food infections. (C) 2016 Elsevier Ltd. All rights reserved.

10aAntibacterial10aBiomimetic synthesis10aGram scale synthesis10aNatural product10aRiboflavin1 aShingare, Rahul, D.1 aFarhana, Sa, Ada1 aReddy, Srinivasa uhttps://library.ncl.res.in/content/multi-gram-scale-synthesis-hunanamycin-antibiotic-natural-product-marine-source01454nas a2200241 4500008004100000245012100041210006900162260000800231300001200239490000800251520062500259100001800884700002400902700001700926700001900943700001500962700002700977700002401004700002001028700002401048700002101072856011901093 2016 eng d00aRepurposing of a drug scaffold: identification of novel sila analogues of rimonabant as potent antitubercular agents0 aRepurposing of a drug scaffold identification of novel sila anal cOCT a723-7300 v1223 a

The structural similarity between an MmpL3 inhibitor BM212, and a cannabinoid receptor modulator rimonabant, prompted us to investigate the anti-tubercular activity of rimonabant and its analogues. Further optimization, particularly through incorporation of silicon into the scaffold, resulted in new compounds with significant improvement in anti-tubercular activity against Mycobacterium tuberculosis (H37Rv). The sila analogue 18a was found to be the most potent antimycobacterial compound (MIC, 31 ng/mL) from this series with an excellent selectivity index. (C) 2016 Elsevier Masson SAS. All rights reserved.

1 aRamesh, Remya1 aShingare, Rahul, D.1 aKumar, Vinod1 aAnand, Amitesh1 aSwetha, B.1 aVeeraraghavan, Sridhar1 aViswanadha, Srikant1 aUmmanni, Ramesh1 aGokhale, Rajesh, S.1 aReddy, Srinivasa uhttps://library.ncl.res.in/content/repurposing-drug-scaffold-identification-novel-sila-analogues-rimonabant-potent01247nas a2200169 4500008004100000245024800041210006900289260000800358300001400366490000900380520046500389100002400854700002500878700002500903700002100928856012800949 2017 eng d00aRoute to benzimidazol-2-ones via decarbonylative ring contraction of quinoxalinediones: application to the synthesis of flibanserin, A drug for treating hypoactive sexual desire disorder in women and marine natural product hunanamycin analogue0 aRoute to benzimidazol2ones via decarbonylative ring contraction  cAUG a5137-51410 v 2 3 a

A simple and practical method to access a variety of benzimidazol-2-ones is reported here. A series of N-alkylsubstituted benzimidazol-2-ones were synthesized by decarbonylative ring contraction starting from corresponding quinoxalinediones for the first time. The utility of the method has been demonstrated by synthesizing recently approved controversial drug flibanserin (Addyi) and a urea analogue of marine antibiotic natural product hunanamycin-A.

1 aShingare, Rahul, D.1 aKulkarni, Akshay, S.1 aSutar, Revannath, L.1 aReddy, Srinivasa uhttps://library.ncl.res.in/content/route-benzimidazol-2-ones-decarbonylative-ring-contraction-quinoxalinediones-application01081nas a2200169 4500008004100000022001400041245009100055210006900146260000800215300001400223520047100237100002500708700002400733700002100757700002100778856011200799 2018 eng d a1434-193X00aTotal synthesis of an anticancer natural product (+/-)-peharmaline A and its analogues0 aTotal synthesis of an anticancer natural product peharmaline A a cDEC a6453-64563 a

First total synthesis of a rare beta-carboline-vasicinone hybrid alkaloid (+/-)-peharmaline A has been accomplished in just 3 steps starting from known compounds. Stereoselective Pictet-Spengler reaction to nitrogenated tertiary carbon center and one-pot construction of the tricyclic skeleton of vasicinone are the highlights of present synthesis. We have also synthesized structurally close analogues of the natural product by following the developed route.

1 aKulkarni, Akshay, S.1 aShingare, Rahul, D.1 aDandela, Rambabu1 aReddy, Srinivasa uhttps://library.ncl.res.in/content/total-synthesis-anticancer-natural-product-peharmaline-and-its-analogues01448nas a2200229 4500008004100000022001400041245009700055210006900152260000800221300001100229490000800240520064800248653003100896653001800927653002400945653001500969653003600984100002401020700002401044700002101068856012901089 2022 eng d a0223-523400aAntibiotic natural product hunanamycin A: Lead identification towards anti-Salmonella agents0 aAntibiotic natural product hunanamycin A Lead identification tow cJUN a1142450 v2363 a

Design and synthesis of library of compounds around the antibiotic natural product hunanamycin A scaffold and their biological evaluation are disclosed here. These efforts resulted in identification of a lead compound 36, which is a structurally simplified analogue of original hunanamycin A with impressive activity against Salmonella enterica and possesses other druggable properties. In addition, no acute oral toxicity was observed for compound 36 in Swiss albino mice dosed up to 2 g/kg. It has the potential to be developed for the treatment of food infections caused by Salmonella. (c) 2022 Published by Elsevier Masson SAS.

10aAntibiotic natural product10aHunanamycin A10aRiboflavin synthase10aSalmonella10aStructure activity relationship1 aShingare, Rahul, D.1 aMacMillan, John, B.1 aReddy, Srinivasa uhttps://library.ncl.res.in/content/antibiotic-natural-product-hunanamycin-lead-identification-towards-anti-salmonella-agents02221nas a2200313 4500008004100000022001400041245010600055210006900161260000800230300001100238490000700249520122400256653001501480653000801495653001101503653002201514653003601536653002001572100002501592700002101617700002401638700001901662700001901681700001601700700001701716700002101733700002101754856013201775 2023 eng d a0968-089600aIdentification of new modulator of DNA repairing pathways based on natural product (±)-peharmaline A0 aIdentification of new modulator of DNA repairing pathways based  cAUG a1173650 v913 a

The complex heterogenic environment of tumour mass often leads to drug resistance and facilitate chemo insensitivity triggering more malignant phenotypes among cancer patients. Major DNA-damaging cancer drugs have been consistently proven unsuccessful in terms of elevating chemo-resistance. (& PLUSMN;)-peharmaline A, a hybrid natural product isolated from seeds of Peganum harmala L. possesses significant cytotoxic activities. Herein, we have described the design, and synthesis of a novel library of close and simplified analogues around the anticancer natural product (& PLUSMN;)-peharmaline A and investigated their cytotoxic activities, which led to the identification of three structurally simplified lead compounds exhibiting better potency than parent natural product. Among them, demethoxy analogue of peharmaline A was further investigated for its anticancer potential eliciting demethoxy analogue as potent DNA-damage inducing agent attenuating the expression of the proteins responsible for the DNA damage repair. Therefore, this demethoxy analogue warrants detailed investigations for the confirmations of the molecular mechanism-based studies responsible for its anticancer activity.

10aDNA damage10aEMT10aPictet10aSpengler reaction10aStructure-activity relationship10aTotal synthesis1 aKulkarni, Akshay, S.1 aDash, Anshurekha1 aShingare, Rahul, D.1 aChand, Jagdish1 aManhas, Diksha1 aSingh, Aman1 aNandi, Utpal1 aGoswami, Anindya1 aReddy, Srinivasa uhttps://library.ncl.res.in/content/identification-new-modulator-dna-repairing-pathways-based-natural-product-%C2%B1-peharmaline02594nas a2200349 4500008004100000022001400041245019200055210006900247260000900316300001100325490000800336520142000344653001501764653001001779653002001789653002001809653002101829653001701850100001801867700002001885700001801905700002101923700002401944700002301968700001901991700002202010700001602032700002402048700002402072700002102096856012702117 2023 eng d a0223-523400aSynthesis, biological evaluation and docking studies of silicon incorporated diarylpyrroles as MmpL3 inhibitors: an effective strategy towards development of potent anti-tubercular agents0 aSynthesis biological evaluation and docking studies of silicon i cNOV  a1156330 v2593 a

Growing global demand for new molecules to treat tuberculosis has created an urgent need to develop novel strategies to combat the menace. BM212 related compounds were found to be potent anti-TB agents and they inhibit mycolic acid transporter, MmpL3, a known potent drug target from Mycobacterium tuberculosis. In order to enhance their inhibitory potency, several silicon analogues of diarylpyrroles related to BM212 were designed, synthesized, and evaluated for anti-tubercular activities. In Alamar blue assay, most of the silicon-incorporated compounds were found to be more potent than the parent compound (BM212), against Mycobacterium tuberculosis (MIC = 1.7 & mu;M, H37Rv). Docking results from the crystal structure of MmpL3 and silicon analogues as pharmacophore model also strongly correlate with the biological assays and suggest that the incorporation of silicon in the inhibitor scaffold could enhance their potency by stabilizing the hydrophobic residues at the binding pocket. The best docking hit, compound 12 showed an MIC of 0.1 & mu;M against H37Rv with an acceptable in vitro ADME profile and excellent selectivity index. Overall, the present study indicates that, the designed silicon analogues, especially compound 12 could be a good inhibitor for an intrinsically flexible drug-binding pocket of MmpL3 and has potential for further development as anti-tubercular agents.

10aantibiotic10aBM21210adocking studies10aMmpL3 inhibitor10aSilicon analogue10atuberculosis1 aVasudevan, N.1 aMotiwala, Zenia1 aRamesh, Remya1 aWagh, Sachin, B.1 aShingare, Rahul, D.1 aKatte, Revansiddha1 aAnand, Amitesh1 aChoudhary, Sushil1 aKumar, Ajay1 aGokhale, Rajesh, S.1 aKulkarni, Kiran, A.1 aReddy, Srinivasa uhttps://library.ncl.res.in/content/synthesis-biological-evaluation-and-docking-studies-silicon-incorporated-diarylpyrroles