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Indanocine, a potent anticancer investigational drug of National Cancer Institute‐USA, has been much discussed in recent years. Present communication aimed at total synthesis of indanocine and its close analogues. Total synthesis was improved by double yields than previously reported yields. Some of the benzylidene and 2‐benzyl derivatives with free rotation at C2 position exhibited potential cytotoxicities against various human cancer cell lines. Five such analogues exhibited potential antiproliferative effect against HCT‐116 and MIA PACA‐2 cell lines. Benzylindanocine 12i induced microtubule destabilization by occupying colchicine binding pocket of β‐tubulin. It also exhibited anti‐inflammatory activity by down‐regulating IL‐6 and TNF‐α. In Ehrlich ascites carcinoma model, 12i reduced 78.4% of EAC tumour in Swiss albino mice at 90 mg/kg (i.p.) dose. Further, in in vivo safety studies, 12i was found to be safe to rodents up to 1,000 mg/kg dose. Concomitant anticancer and anti‐inflammatory activity of benzylindanocine is distinctive, which suggests its further optimization for better efficacy and druggability. [ABSTRACT FROM AUTHOR]

Novel Mannich base derivatives of glabridin were synthesized and their antiproliferative activity were performed along with our previously reported glabridin-chalcone hybrids molecules (GCHMs) against various human cell lines MDA-MB-231 (breast adenocarcinoma), HEK-293 (embryonic kidney cell line), K562 (leukemia), MCF-7 (breast adenocarcinoma), HeLa (cervix adenocarcinoma), HepG2 (hepatocellular carcinoma) and WRL-68 (hepatic carcinoma). The result showed that the glabridin significantly reduced cell proliferation with IC50 ranges from 3.67 to 58.30 µM against all the tested cell lines. The remarkable reduction in antiproliferative activity 2',4'-dimethoxyglabridin and GCHMs compounds with phenolic OH groups protected by methoxy (OCH3) groups suggested that the free OH groups are essential factor for the antiproliferative activity of glabridin and its derivatives. The Mannich base derivatives of glabridin showed moderate activity IC50 (2.20–>95.78 µM). Furthermore, in silico target identification analysis revealed that AKT1, DECR1 and NOS1 are the potential targets for glabridin and their derivatives. [ABSTRACT FROM AUTHOR]

Prostate cancer is fourth most abundant cancer type around the globe. Brevifoliol, a rearranged taxoid from Taxus walllichiana needles has been derivatized as C5 esters using Steglich esterification reaction. Seventeen diverse analogues were evaluated against a panel of human cancer cell lines by MTT assay. Among these, two of the semi‐synthetic analogues, that is, 13 and 16 exhibited potent cytotoxicity, selectively against PC‐3, prostate cancer cell lines. In cell cycle analysis, analogue 13 induced S and G2/M phase arrest and induced apoptosis by activating caspase‐3. Compound 13 showed moderate efficacy in in‐vivo Ehrlich ascites carcinoma in Swiss albino mice. Further, compound 13 was found to be safe in Swiss albino mice up to 1,000 mg/kg dose in acute oral toxicity. Brevifoliol ester 13 may further be optimized for better efficacy. [ABSTRACT FROM AUTHOR]

In the present work, quantitative structure-activity relationship (QSAR) models of camptothecin derivatives against DNA Topoisomerase-I (DNA Topo-I) were developed by multiple linear regression method using leave-one-out validation approach. The r2 and rCV2 of the model were 0.89 and 0.86, respectively. The QSAR study indicates that chemical descriptors, namely Connectivity Index (order 1, standard), Electron Affinity (eV), Molecular Weight, Group Count (ether) are correlated well with activity. Further, screening for drug likeness, ADME and toxicity showed that compound CPT9, CPT14, CPT20, CPT21 and CPT22 exhibits marked anticancer activity and possesses two times more potent than standard drug camptothecin. The docking study showed a high binding affinity of predicted active derivatives and showed H-bond formation with GLY363, ARG364, LYS374, GLN421, ARG488, and ASP-533 residues, therefore considered as more stable and potent anticancer compounds. The obtained results can be used for the design of novel potent and selective inhibitors of DNA Topo-I. Copyright © 2013 John Wiley & Sons, Ltd. [ABSTRACT FROM AUTHOR]

[Display omitted] Receptors are proteinous macromolecules which remain in the apo form under normal/unliganded conditions. As the ligand approaches, there are specific stereo-chemical changes in the apo form of the receptor as per the stereochemistry of a ligand. Accordingly, a series of substituted dimethyl-chroman-based stereochemically flexible and constrained Tamoxifen analogs were synthesized as anti-breast cancer agents. The synthesized compounds 19a-e, 20a-e, 21, and 22a-e, showed significant antiproliferative activity against estrogen receptor-positive (ER+, MCF-7) and negative (ER-, MDA MB-231) cells within IC 50 value 8.5–25.0 µM. Amongst all, four potential molecules viz 19b , 19e , 22a , and 22c , were evaluated for their effect on the cell division cycle and apoptosis of ER+ and ER- cancer cells (MCF-7 & MDA MB-231cells), which showed that these compounds possessed antiproliferative activity through triggering apoptosis. In-silico docking experiments elucidated the possible affinity of compounds with estrogen receptors-α and -β. [ABSTRACT FROM AUTHOR]

Prostate cancer is one of the most common cancers in men. Diosgenin and related compounds are potential cytotoxic agents. Twelve diverse analogues of long chain fatty acid/ester of diosgenin-7-ketoxime have been prepared. Six of the analogues exhibited significant anticancer activity against a panel of human cancer cell lines with IC 50 ranging from 12 to 35 μM. Compound 16 , the best representative of the series exerted S phase arrest in DU145 prostate cancer cells and induced apoptosis through caspase pathway. Additionally, these analogues inhibited lipopolysaccharide induced pro-inflammatory cytokines (TNF-α and IL-6) up to 47.7% and 23.3% respectively. Compound 16 was found to be safe in acute oral toxicity in Swiss albino mice up to 300 mg/kg dose. The anticancer and antiinflammatory properties of compound 16 are important and can further be optimized for a better anti-prostate cancer candidate. [ABSTRACT FROM AUTHOR]

Different alkyl amide ( 15a – l ) and alkyl amine ( 16a – e ) derivatives of 7,8-dimethoxy-3-hydroxy-2-(4-methoxyphenyl)benzopyran-4-one were synthesized and evaluated for their anticancer activity against five different cancer cell lines using SRB assay. Compounds 15e , 15i , 15j and 16a – e showed significant anticancer activity within the range of IC 50 2.58–34.86 μM. The most promising molecule, 1 6c , was further analyzed for its effect on cell cycle and apoptosis of estrogen receptor positive cancer cells (MCF-7 cells) which showed that 16c triggered apoptosis in MCF-7 cells and arrested cells population at sub-G 0 (apoptotic) and G 2 M phase. In tubulin polymerization assay, 16c interfered with kinetics of tubulin polymerization. [ABSTRACT FROM AUTHOR]

2-Methoxyestradiol (2ME 2 ), an estrogen hormone metabolite is a potential cancer chemotherapeutic agent. Presently, it is an investigational drug under various phases of clinical trials alone or in combination therapy. Its anticancer activity has been attributed to its antitubulin, antiangiogenic, pro-apoptotic and ROS induction properties. This anticancer drug candidate has been explored extensively in last twenty years for its detailed chemistry and pharmacology. Present review is an update of its chemistry and biological activity. It also extends an assessment of potential of 2ME 2 and its analogues as possible anticancer drug in future. [ABSTRACT FROM AUTHOR]

Diosgenin has been modified to furostane derivatives after opening the F-spiroacetal ring. The aldehyde group at C26 in derivative 8 was unexpectedly transformed to the ketone 9. The structure of ketone 9 was confirmed by spectroscopy and finally by X-ray crystallography. Five of the diosgenin derivatives showed significant anticancer activity against human cancer cell lines. The most potent molecule of this series i.e. compound 7, inhibited cellular growth by arresting the population at G0/G1 phase of cell division cycle. Cells undergo apoptosis after exposure to the derivative 7 which was evident by increase in sub G0 population in cell cycle analysis. Docking experiments showed caspase-3 and caspase-9 as possible molecular targets for these compounds. This was further validated by cleavage of PARP, a caspase target in apoptotic pathway. Compound 7 was found non-toxic up to 1000mg/kg dose in acute oral toxicity in Swiss albino mice. [ABSTRACT FROM AUTHOR]

Abstract: Tubulin is a well established target for anticancer drug development. Lignans and neolignans were synthesized as tubulin interacting agents. Neolignans 10 and 19 exhibited significant anticancer activity against MCF-7 and MDAMB-231 human breast cancer cell lines. Both the compounds effectively induced stabilization of microtubule at 4 and 20μM concentrations respectively. Neolignan 10 induced G2/M phase arrest in MCF-7 cells. Docking experiments raveled that 10 and 19 occupied the same binding pocket of paclitaxel with some difference in active site amino acids and good bioavailability of both the compounds. In in vivo acute oral toxicity 10 was well tolerated up to 300mg/kg dose in Swiss-albino mice. [Copyright &y& Elsevier]

[Display omitted] Substituted amide derivatives of C4-ageratochromene dimer analog (19) were synthesized through structural modification of precocene-I (4a), isolated from the essential oil of Ageratum conyzoides L. The target compounds (18 – 20 , 23I-VI , 24I-VI, and 25I-VI) were evaluated for their bone-forming effect using osteoblast differentiation assay. Seven compounds (23I, 23II, 23IV, 23VI, 24III, 24VI, and 25VI) presented good activity within 1 pM–1 nM concentration. At 1 pM concentration, the most active compound i.e. 23II showed effective mineralization of osteoblast cells along with expression of osteogenic marker genes viz RUNX 2, BMP-2, and type 1 collagen (Type-1 col) without any toxicity towards osteoblast cells. Single crystal X-ray analysis of 18 and 20 revealed that the core nucleus of these molecules bear phenyl rings in a Trans -stilbenoid system and had a good structural correlation with 17β-estradiol (1) and diethylstilbestrol (DES, 3). In-silico study about 23II showed its structural complementarities with the LBD of estrogen receptor (ER) which indicated possible ER-mediated activity of compounds. [ABSTRACT FROM AUTHOR]

• An extensive cancer pharmacology of Fluorinated benzylidene indanone has been explored. • Induces late apoptosis in breast cancer cells (MCF-7 & MDA-MB-231). • Occupies colchicine binding pocket of β-tubulin. • Down-regulates tumour angiogenic factors; VEGF and HIF-α in MCF-7 cells. • In-vivo efficacy: 48.2% tumour reduction at 120 mg/kg oral dose. • Safety: in-vivo acute toxicity- safe up to 1000 mg/kg dose. The application of fluorine in drug design has been understood significantly by the medicinal chemists in recent years. Modulation of tubulin-microtubule dynamics is one of the most effective targets for cancer chemotherapeutics. A logically designed and identified lead compound, fluorinated benzylidene indanone 1 has been extensively evaluated for cancer pharmacology. It occupied colchicine binding pocket acting as microtubule destabilizer and induced a G2/M phase arrest in MCF-7 cells. Compound 1 exerted an antiangiogenic effect in MCF-7 cells by down-regulating Vascular Endothelial Growth Factor (VEGF) and Hypoxia Inducible Factor-α (HIF-α). In in-vivo efficacy in C3H/Jax mice mammary carcinoma model, benzylidene indanone 1 reduced tumour volumes by 48.2%. Further in acute oral toxicity studies compound 1 was well tolerated and safe up to 1000 mg/kg dose in Swiss albino mice. The fluorinated benzylidene indanone 1 , a new chemical entity (NCE) can further be optimized for better efficacy against breast adenocarcinoma. 1 1 CSIR-CIMAP Communication no. 2020-FEB/13 To create your abstract, type over the instructions in the template box below. Fonts or abstract dimensions should not be changed or altered. Image, graphical abstract [ABSTRACT FROM AUTHOR]

A series of amide derivatives of stilbene was synthesized and investigated for osteogenic activity. Out of sixteen, seven compounds viz 19c , 19g , 19i , 24b , 25a , 25c and 26a showed significant osteoblast differentiation within 1 pM–1 µM concentrations. Amongst all, 26a was identified as most active molecule which presented effective mineralization of osteoblasts and expression of mRNA of osteogenic marker gene such as BMP-2, ALP, and Runx-2 at 1 pM. In estrogen-deficient balb/c mice, 26a showed significant osteogenic activity at 5 mg-kg−1 body weight dose. The protein expression study for estrogen receptors α and β (ER-α & ER-β) using mouse calvarial osteoblasts (MCOs) and molecular docking analyses showed preferential expression of ER-β by 26a indicating the possibility of ER-β mediated osteogenic activity of 26a. [ABSTRACT FROM AUTHOR]

Carbamate derivative at C26 of furostene ring after opening spiroketal bond (F-ring) of diosgenin exhibits potent anticancer activity against breast Cancer. • C26-furostene carbamates have been prepared from Diosgenin. • Carbamate 10 , antiproliferative against TNBC (IC 50 = 13.5 μM) induces apoptosis by activation of caspase pathway. • Concomitant antiproliferative and antiinflammatory property as well is important. • Efficacy: In-vivo anticancer activity 65.4% tumour reduction at 75 mg/kg dose. • Safety: In-vivo acute toxicity- safe up to 300 mg/kg dose. Breast cancer is the most prevalent cancer in women affecting about 12% of world's female population. It is a multifactorial disease, mostly invasive in nature. Diosgenin and related compounds are potent antiproliferative agents. Carbamate derivatives have been synthesized at C26 of furostene ring after opening spiroketal bond (F-ring) of diosgenin. Compound 10 possessed significant antiproliferative activity against human breast cancer cells by arresting the population at G1 phase of cell division cycle and induced apoptosis. Induction of apoptosis was observed through the caspase signalling cascade by activating caspase-3. Moreover, carbamate 10 exhibited moderate antiinflammatory activity by decreasing the expression of cytokines, TNF-α and IL-6 in LPS-induced inflammation in primary macrophage cells. Furthermore, compound 10 significantly reduced Ehrlich ascites carcinoma significantly in mice. It was well tolerated and safe in acute oral toxicity in Swiss albino mice. The concomitant anticancer and antiinflammatory properties of carbamate 10 are important and thus, can further be optimized for a better anti-breast cancer candidate. [ABSTRACT FROM AUTHOR]