00784nas a2200217   4500008004100000245009400041210006900135260000800204300001400212490000700226100003500233700002400268700002200292700002400314700001900338700001800357700002000375700002700395700002100422856012300443       2016                        eng d00aIdentification of noreremophilane-based inhibitors of angiogenesis using zebrafish assays0 aIdentification of noreremophilanebased inhibitors of angiogenesi  cOCT  a1569-15780 v141 aMuthukumarasamy, Kalai, Mangai1 aHandore, Kishor, L.1 aKakade, Dipti, N.1 aShinde, Madhuri, V.1 aRanjan, Shashi1 aKumar, Naveen1 aSehrawat, Seema1 aSachidanandan, Chetana1 aReddy, Srinivasa  uhttps://library.ncl.res.in/content/identification-noreremophilane-based-inhibitors-angiogenesis-using-zebrafish-assays01669nas a2200217   4500008004100000245012500041210006900166260000800235300001400243490000700257520088500264100002101149700002301170700002201193700002101215700002501236700001901261700002101280700002001301856013001321       2017                        eng d00aIdentification and synthesis of mycalol analogues with improved potency against anaplastic thyroid carcinonia cell lines0 aIdentification and synthesis of mycalol analogues with improved   cAPR  a1125-11330 v803 aThe marine metabolite mycalol (1) has a specific inhibitory activity on cells of anaplastic thyroid carcinoma (ATC), a very aggressive and rare cancer that does not have effective conventional therapy. In this study, we describe six new related analogues (2-7) that differ in the length of the terminal alkyl residue and the presence of acetate or 3S-hydroxybutyrate (3S)-3HB as a substituent at C-19. Despite the structural' analogies, some of the new members were significantly more-cytotokic than 1 on cell lines,derivecl from human ATC. Structures inclusive of the 2'R,3R,4S,7R,8S,19R absolute configuration were asigned to 2-7 on the basis of detailed spectroscopic analysis, synthesis of different isomers, and application of ECD and Mosher's methods. This work led to the identification of mycal61-578 (3) as the most potent analogue, with an IC50 of 2.3 mu M on FRO cells:1 aCutignano, Adele1 aSeetharamsingh, B.1 aD'Angelo, Daniela1 aNuzzo, Genoveffa1 aKhairnar, Pankaj, V.1 aFusco, Alfredo1 aReddy, Srinivasa1 aFontana, Angelo  uhttps://library.ncl.res.in/content/identification-and-synthesis-mycalol-analogues-improved-potency-against-anaplastic-thyroid02000nas a2200193   4500008004100000245011000041210006900151260000800220300001100228490000800239520128500247100003101532700002701563700002701590700002101617700001801638700002101656856012901677       2017                        eng d00aIdentification of new anti-inflammatory agents based on nitrosporeusine natural products of marine origin0 aIdentification of new antiinflammatory agents based on nitrospor  cJUL  a89-1090 v1353 aNitrosporeusines A and B are two recently isolated marine natural products with novel skeleton and exceptional biological profile. Interesting antiviral activity of nitrosporeusines and promising potential in curing various diseases, evident from positive data from various animal models, led us to investigate their anti-inflammatory potential. Accordingly, we planned and synthesized nitrosporeusines A and B in racemic as well as enantiopure forms. The natural product synthesis was followed by preparation of several analogues, and all the synthesized compounds were evaluated for in vitro and in vivo anti-inflammatory potential. Among them, compounds 25, 29 and 40 significantly reduced levels of nitric oxide (NO), reactive oxygen species (ROS) and pro-inflammatory cytokines. In addition, these compounds suppressed several pro-inflammatory mediators including inducible nitric oxide synthase (iNOS), cyclooxygenase-2 (COX-2), nuclear factor-kappa B (NF -kappa B), and thereby can be emerged as potent anti-inflammatory compounds. Furthermore, all possible isomers of lead compound 25 were synthesized, characterized and profiled in same set of assays and found that one of the enantiomer (-)-25a was superior among them. (C) 2017 Elsevier Masson SAS. All rights reserved.1 aPhilkhana, Satish, Chandra1 aVerma, Abhishek, Kumar1 aJachak, Gorakhnath, R.1 aHazra, Bibhabasu1 aBasu, Anirban1 aReddy, Srinivasa  uhttps://library.ncl.res.in/content/identification-new-anti-inflammatory-agents-based-nitrosporeusine-natural-products-marine01750nas a2200229   4500008004100000245008100041210006900122260000800191300001600199490000600215520098800221100002501209700001801234700001701252700002501269700002601294700003001320700001801350700002301368700002101391856010801412       2021                        eng d00aIdentification of a novel series of potent organosilicon mosquito repellents0 aIdentification of a novel series of potent organosilicon mosquit  cNOV  a31236-312430 v63 aMosquito control by personal protection is one of the most efficient ways of curtailing deadly diseases such as malaria and dengue with the potential to save millions of lives per year. DEET (N,N-diethyl-3-methyl benzamide) is currently considered as the gold standard for mosquito repellents, being used for the past several decades. Control by DEET, however, is being threatened by emerging resistance among mosquitoes. To address this concern and also to improve protection times, we synthesized a novel series of 25 silicon-containing acyl piperidines using acid–amine coupling protocol and tested their activity against Aedes aegypti in mosquito-repellent assays. Several compounds from this series appear to possess good mosquito-repellent properties. Most notably, at 0.5 mg/cm2 concentrations, the mean protection time for NDS100100 was 756 min, which was higher than that of DEET (616 min). The details of design, synthesis, and biological evaluation are discussed herein.1 aKulkarni, Akshay, S.1 aRamesh, Remya1 aWalia, Safal1 aSayyad, Shahebaz, I.1 aGathalkar, Ganesh, B.1 aBalamkundu, Seetharamsing1 aJoshi, Manali1 aSen, Avalokiteswar1 aReddy, Srinivasa  uhttps://library.ncl.res.in/content/identification-novel-series-potent-organosilicon-mosquito-repellents02221nas 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<p>
	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. (&amp; 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 (&amp; 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.</p>
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-peharmaline02942nas a2200289   4500008004100000022001400041245011000055210006900165260000800234300001100242490000800253520203200261653000802293653000902301653001602310653001502326653001002341100002102351700002502372700001902397700002602416700001902442700001702461700002102478700002102499856013202520       2025                        eng d  a1567-576900aInterplay between genotoxic stress and STING activation in cellular senescence and inflammatory responses0 aInterplay between genotoxic stress and STING activation in cellu  cOCT  a1153710 v1643 a<p>
	STING pathway is activated by endogenous or exogenous DNA damage and is known to trigger cell-intrinsic innate immunity. In this study, we demonstrated that the Peharmaline analog NDS101781 is a potent genotoxic molecule to trigger cellular senescence via innate immune-responsive STING activation. We found NDS101781 consistently modulated the expression of DDR markers including gamma-H2AX, Rad51, PARP1, ATM and MRE11 in breast cancer cells with concomitant amplification in the hallmarks of senescence along with STING signaling mediators which is intricately involved in NDS101781-mediated senescence activation as evidenced by significant reduction in the senescent population in si-TMEM173-transfected cells. In vitro findings proclaimed that STING activation by NDS101781 is crucial for p21-mediated senescence augmentation, a process regulated by ATM and p53 via a pathway independent of cGAS. Although STING is activated by both canonical and non-canonical manner, our mechanistic findings indicated that ATM played a crucial role in early activation of NDS101781 driven STING signaling via p53 activation and stimulation of pTBK1, NF-kappa B, and p-IRF3, through a non-canonical cascade in cGAS-independent mechanism. The results also indicated that interference of canonical and non-canonical STING activation, responsible for NF-kappa B stimulation leading to IL-6 generation. Intriguingly, the inhibition of ATM diminished senescence hallmarks; however, suppression of ATM as well as p21 neutralization triggered apoptotic cascade and thus regulating the SASP factors. However, transient knockdown of p21 moderately instigated the apoptotic mediators underscoring that NDS101781 mediated senescence induction delayed programmed cell death under intact p21 conditions. Moreover, pharmacokinetics of NDS101781 confirmed its excellent half-life in a preclinical model and in vivo studies confirmed that NDS101781 significantly inhibited tumor growth in a syngeneic aggressive 4T1-p53 breast cancer model.</p>
10aATM10aIL-610aPeharmaline10aSenescence10aSTING1 aDash, Anshurekha1 aKulkarni, Akshay, S.1 aIrshad, Faisal1 aMasal, Dattatraya, P.1 aManhas, Diksha1 aNandi, Utpal1 aReddy, Srinivasa1 aGoswami, Anindya  uhttps://library.ncl.res.in/content/interplay-between-genotoxic-stress-and-sting-activation-cellular-senescence-and-inflammatory