Sabina Yasmin

Synthesis, Characterisation, and In Vitro Anticancer Activity of Curcumin Analogues Bearing Pyrazole/Pyrimidine Ring Targeting EGFR Tyrosine Kinase

In search of potential therapeutics for cancer, we described herein the synthesis, characterization, and in vitro anticancer activity of a novel series of curcumin analogues. The anticancer effects were evaluated on a panel of 60 cell lines, according to the National Cancer Institute (NCI) screening protocol. There were 10 tested compounds among 14 synthesized compounds, which showed potent anticancer activity in both one-dose and 5-dose assays. The most active compound of the series was 3,5-bis(4-hydroxy-3-methylstyryl)-1H-pyrazole-1-yl(phenyl)methanone (10) which showed mean growth percent of −28.71 in one-dose assay and GI50 values between 0.0079 and 1.86 µM in 5-dose assay.

Thiazolidinediones and PPAR orchestra as antidiabetic agents: From past to present

Thiazolidinediones a class of drug, that provided a major breakthrough in the management of type 2 diabetes since 1990. Following the discovery of PPARs, TZDs were the first class to be reported as PPARγ modulators. This review is an attempt to summarize the chemical modifications around TZDs in past two decades to obtain a potent antidiabetic molecule. TZDs literature were initially dominated by their hypoglycemic & hypolipidemic activities, later PPARγ activity was also been incorporated. Moreover, in some cases, both benzyl and benzylidene derivatives were reported in the same manuscript for the sake of comparison. We thought of presenting the review on the basis of the variation in the linker region. Optimal linker at the time of discovery of the Ciglitazone was oxymethyl and it went on to evolve as oxyethyl (Pioglitazone) and oxyethylamino (Rosiglitazone). Few attempts were made to restrict the flexibility of the linker by introducing the cyclic structures and were summarized immediately after the respective linker class.

Structure based molecular design, synthesis and biological evaluation of α-pyrone analogs as anti-HSV agent.

Several options for treating Herpes Simplex Virus type 1 and type 2 are available. However, non-specific inhibition and drug resistance warrants the discovery of new anti-herpetic compounds with better therapeutic profile or different mode of action. The non-nucleoside inhibitors of HSV DNA polymerase target the site that is less important for the binding of a natural nucleoside or nucleoside inhibitors. In the present study, we have explored the possibility to find a new lead molecule based on α-pyrone analogs as non-nucleoside inhibitors using structure based modeling approach. The designed molecules were synthesized and evaluated for anti-HSV activity using MTT assay. The compound 5h with EC(50) 7.4μg/ml and CC(50) 52.5μg/ml was moderately active against HSV when compared to acyclovir. A plaque reduction assay was also carried out and results reveal that 5h is more effective against HSV-1 with better selective index of 12.8 than against HSV-2 (SI=3.6). The synthesized compounds were also evaluated for anti-HIV activity, but none were active.

Synthesis and anticancer activity of N-aryl-5-substituted-1,3,4-oxadiazol-2-amine analogues.

In continuance of our search for anticancer agents, we report herein the synthesis and anticancer activity of some novel oxadiazole analogues. The compounds were screened for anticancer activity as per National Cancer Institute (NCI US) protocol on leukemia, melanoma, lung, colon, CNS, ovarian, renal, prostate, and breast cancers cell lines. N-(2,4-Dimethylphenyl)-5-(4-methoxyphenyl)-1,3,4-oxadiazol-2-amine (4s) showed maximum activity with mean growth percent (GP) of 62.61 and was found to be the most sensitive on MDA-MB-435 (melanoma), K-562 (leukemia), T-47D (breast cancer), and HCT-15 (colon cancer) cell lines with GP of 15.43, 18.22, 34.27, and 39.77, respectively. Maximum GP was observed on MDA-MB-435 (melanoma) cell line (GP = 6.82) by compound N-(2,4-dimethylphenyl)-5-(4-hydroxyphenyl)-1,3,4-oxadiazol-2-amine (4u).

Synthesis, Anticancer and Molecular Docking Studies of2-(4-chlorophenyl)-5-aryl-1,3,4-Oxadiazole Analogues

Among a series of ten, 2-(4-chlorophrnyl)-5-aryl-1,3,4-oxadiazole analogs, 4c showed maximum activity on various cancer cell lines, with average growth percent of 95.37%. The molecular docking studies for the compounds 4a & 4c showed that the residue Cys797 is present near to the para substitution of phenyl group while the five member oxadiazole ring of ligandswas lying near to Leu792 and Met 793 of EGFR tyrosine kinase active

Synthesis and Antiproliferative Activity of Some Quinoline and Oxadiazole Derivatives

In continuance of our search for newer antiproliferative agents we report herein the synthesis and antiproliferative studies of two series (5a–j and 10a–c) of heterocyclic compounds. All the new compounds were characterized by IR, NMR, and mass spectral data. The antiproliferative activity of 10 compounds (5a–j) was carried out on HeLa (cervix cancer cell line) and MDA-MB-435 (melanoma) and LC50, TGI, and GI50 were calculated, while the antiproliferative activity of 3 compounds (10a–c) was carried out against nine different panels of nearly 60 cell lines (NCI-60) according to the National Cancer Institute (NCI US) Protocol at 10 μM. 1-(7-Hydroxy-4-methyl-2-oxoquinolin-1(2H)-yl)-3-(4-methoxylphenyl)urea (5j) was found to have antiproliferative activity with GI50 of 35.1 μM against HeLa (cervix cancer cell line) and 60.4 μM against MDA-MB-435 (melanoma), respectively. The compounds 10a, 10b, and 10c showed antiproliferative activity with comparatively higher selectivity towards HOP-92 (Non-Small Cell Lung Cancer) with percent growth inhibitions (GIs) of 34.14, 35.29, and 31.59, respectively.

Design and synthesis of new 2,5-disubstituted-1,3,4-oxadiazole analogues as anticancer agents

In continuance of our search for new anticancer agents, we report herein the design, synthesis, and anticancer evaluation of oxadiazole analogues. Two series (4a-h and 4i-q) of new oxadiazole analogues were designed based on heterocyclic (1,3,4-oxadiazole)-linked aryl core of IMC-038525 (tubulin polymerization inhibitor), NSC 776715, and NSC 776715 and synthesized. All the compounds were fully characterized by infrared, nuclear magnetic resonance spectroscopy, and mass spectral data and the purity of compounds was checked by elemental analysis (C, H, and N analysis). Further seven compounds were evaluated for anticancer activity on nine different panels of 60 cell lines (60 NCI cancer cell lines) according to the National Cancer Institute screening protocol and percent growth and percent growth inhibition was calculated at 10 µM drug concentration. Ten compounds were evaluated for anticancer activity on two cancer cell lines (HeLa and MDA-MB-435) as per the standard protocol reported at four different drug concentrations (10−7, 10−6, 10−5, and 10−4 µM) and GI50, LC50, and TGI dose-related parameters were calculated. The compound 4j showed maximum anticancer activity at 10 µM, and was found to have higher sensitivity against MOLT-4, IGROV1, HCT-116, and K-562 with percent growth inhibitions of 50.38, 48.45, 46.26, and 46.26 respectively. The compound 4j showed superior anticancer activity than imatinib on 41 human cancer cell lines. The compound 4p showed anticancer activity with GI50 of 36.7 and 46.5 µM against HeLa and MDA-MB-435 cell lines, respectively.

Novel Benzylidene Thiazolidinedione Derivatives as Partial PPARγ Agonists and their Antidiabetic Effects on Type 2 Diabetes

Peroxisome proliferator-activated receptor γ (PPARγ) has received significant attention as a key regulator of glucose and lipid homeostasis. In this study, we synthesized and tested a library of novel 5-benzylidene-thiazolidin-2,4-dione (BTZD) derivatives bearing a substituent on nitrogen of TZD nucleus (compounds 1a-1k, 2i-10i, 3a, 6a, and 8a-10a). Three compounds (1a, 1i, and 3a) exhibited selectivity towards PPARγ and were found to be weak to moderate partial agonists. Surface Plasmon Resonance (SPR) results demonstrated binding affinity of 1a, 1i and 3a towards PPARγ. Furthermore, docking experiments revealed that BTZDs interact with PPARγ through a distinct binding mode, forming primarily hydrophobic contacts with the ligand-binding pocket (LBD) without direct H-bonding interactions to key residues in H12 that are characteristic of full agonists. In addition, 1a, 1i and 3a significantly improved hyperglycemia and hyperlipidaemia in streptozotocin-nicotinamide (STZ-NA)-induced diabetic rats at a dose of 36 mg/kg/day administered orally for 15 days. Histopathological investigations revealed that microscopic architecture of pancreatic and hepatic cells improved in BTZDs-treated diabetic rats. These findings suggested that 1a, 1i and 3a are very promising pharmacological agents by selectively targeting PPARγ for further development in the clinical treatment of type 2 diabetes mellitus.