Thiazolobenzamide-Naphthalene Hybrids as Potent Anticancer agents compared to Doxorubicin: Design, Synthesis, SAR, In-silico and Toxicity Analysis.

In order to determine whether thiazolobenzamide molecules connected to naphthalene could inhibit the growth of three different tumor cell lines, MCF7 (breast carcinoma), A549 (pulmonary carcinoma), and DU145 (prostatic adenocarcinoma) a novel series of ten molecules, designated TA 1-10, was designed, synthesized, and tested. Among these compounds, TA7 showed promising results against cell lines, especially showing exceptional efficacy against breast cancer. Antioxidant activity tests consistently showed the best performance from the TA7 molecule. Furthermore, when a dose of 50 to 500 mg/kg of the total mass of rats is given, the most effective chemical, TA7, did not exhibit any harmful effects during acute oral toxicity tests. The biochemical indicators (SGOT and SGPT) for hepatotoxicity associated with compound TA7 were found to be fairly similar to those of the control group. The findings from molecular docking, XP visualization, and MM-GBSA dG binding investigations are in agreement with the outcomes of in-vitro tests of antioxidant and anticancer capabilities. TA7 was the most effective compound among those that were docked; it bound free energy and had adequate properties for metabolism (biochemical processes), distribution (dispersion), absorption (assimilation), and excretion (elimination). This study found that the TA7 molecule, a thiazole ring system derivative connected to naphthalene, is to be a promising and possible anticancer agent and its efficacy may be further explored in clinical studies.

Design, synthesis, and biological evaluation of imidazopyridine-linked thiazolidinone as potential anticancer agents.

In this study, two series of imidazopyridine-linked thiazolidinone rings (5a-h and 6a-h) constituting 16 new compounds were synthesized and tested for their antiproliferative activity against a panel of three human cancer cell lines, that is, MCF-7 (human breast cancer), A549 (human lung cancer), and DU145 (human prostate cancer). Three compounds, 5h, 6f, and 6h, exhibited remarkable results against all three cell lines, but compound 6h was found to be the most active one against the breast cancer cell line. Among all the synthesized compounds, 6h displayed the highest antioxidant results. Furthermore, the potent compounds 5h, 6f, and 6h showed no signs of toxicity at doses ranging from 50 to 500 mg/kg of animal body weight. The biochemical parameters (SGOT and SGPT) of compound 6h nearly matched the control in hepatotoxicity studies. The molecular docking and MM-GBSADG binding studies are in agreement with the in vitro anticancer and antioxidant activity results. The most promising compound 6h was found to have the highest docking score and binding energy, and its absorption, distribution, metabolism, and excretion (ADME) parameters are in the acceptable range. Thus, it can be concluded that 6h, an imidazopyridine derivative endowed with a thiazolidinone ring system, has the potential to be developed as an anticancer agent.

Novel hybrids of benzothiazole-1,3,4-oxadiazole-4-thiazolidinone: Synthesis, in silico ADME study, molecular docking and in vivo anti-diabetic assessment.

A series of new benzothiazole-1,3,4-oxadiazole-4-thiazolidinone hybrid analogs (Tz1-Tz28) were synthesized in search of potential anti-diabetic agents. Molecular docking study was conducted with binding pocket of peroxisome proliferator activated receptor-gamma to elucidate the binding interactions of newly synthesized targets. Seven selected compounds with best docking scores were further screened for in vivo anti-hyperglycemic efficacy by oral glucose tolerance test in non-diabetic rats and on streptozotocin induced diabetic rat models. All the tested compounds demonstrated excellent to moderate reduction in blood glucose levels. Three of the compounds (Tz21, Tz7 and Tz10) showed excellent anti-diabetic effect by reducing concentration of glucose to 157.15 ±â€¯1.79 mg/dL, 154.39 ±â€¯1.71 mg/dL, 167.36 ±â€¯2.45 mg/dL, respectively better than the standard drug, pioglitazone, 178.32 ±â€¯1.88 mg/dL. Moreover, three derivatives Tz21, Tz4 and Tz24 with IC50 values of 0.21 ±â€¯0.01 µM, 9.03 ±â€¯0.12 µM and 11.96 ±â€¯0.40 µM respectively also showed better inhibitory activities on alpha-glucosidase even more than the standard acarbose (IC50 = 18.5 ±â€¯0.20 µM), indicating Tz21 has the highest inhibitory effect among the seven tested derivatives. Prediction of Drug like properties using molinspiration online software suggests that all the synthesized compounds have potential of becoming the orally active molecules. Thus, these novel hybrids could serve as potential candidates to become leads for the development of new drugs eliciting anti-hyperglycemic effect orally.

Synthesis, ADME, docking studies and in vivo anti-hyperglycaemic potential estimation of novel Schiff base derivatives from octadec-9-enoic acid.

A new series of octadec-9-enoic acid schiff base entities (S1-S30) were designed and synthesized targeting peroxisome proliferator activated receptor-gamma for agonist action. Molinspiration software (online) was used to estimate drug like molecular properties of the metabolites. Docking disquisition on co-crystallized protein of PPAR-γ (PDB ID 1FM9) was carried out which showed S21, S10 and S7 as best situated in the vital sites of receptor having docking scores -9.19, -8.68 and -8.64 respectively. Free binding energy measured using model of Maestro 9.0 and was in range of from -40.01 and -80.54 kcal/mol, significant when compared with pioglitazone (-51.58 Kcal/mol). Seven best docked derivatives were assessed for in-vivo oral glucose tolerance on normal rats and anti-hyperglycaemic activity by streptozotocin induced diabetes model. S21 unveiled to be the best measured analogue among all the synthesized entities. Encouraging outcomes motivates fatty acids for further development of more effective and safer compounds.

Synthesis, molecular modelling studies and ADME prediction of benzothiazole clubbed oxadiazole-Mannich bases, and evaluation of their anti-diabetic activity through in vivo model.

A small library of new benzothiazole clubbed oxadiazole-Mannich bases (M-1 to M-22) were synthesized and characterized by IR, NMR, Mass and Elemental analysis results. Molecular docking studies were done to assess the binding mode and interactions of synthesized hits at binding site of receptor Peroxisome proliferator-activated receptor, PPAR-γ or PPARG (PDB 1FM9). Among the synthesized compounds, nine compounds were selected on the basis of docking score and evaluated for their in vivo anti-diabetic activity using Oral Glucose Tolerance Test (OGTT) in normal rats followed by Streptozotocin (STZ) - induced diabetes. Results indicated that compound M-14 (161.39 ±â€¯4.38) showed the highest reduction of blood glucose level comparable to that of the standard drug glibenclamide (140.29 ±â€¯1.24) in STZ model. Other compounds exhibited moderate to good anti hyperglycaemic activity. ADME studies was done using Molinspiration online software, revealed that all compounds (except M-11) are likely to be orally active as they obeyed Lipinski's rule of five.

Insights into the chemistry and therapeutic potential of furanones: A versatile pharmacophore.

Furanone, a five-membered heteroaromatic ring containing oxygen atom, is of immense pharmaceutical importance. Presence of this nucleus in biologically active compounds of natural and synthetic origin has made it an indispensable motif for design and development of new therapeutic agents. In recent years synthesis of furanone derivatives and exploring their therapeutic actions has been the prime interest amongst researchers. Furanone containing compounds cover numerous therapeutic categories viz. Analgesic and anti-inflammatory, anticancer, anticonvulsant, antibacterial and antifungal, antioxidant, antiulcer and anti-TB, etc. There is a need to couple recent work done with previously available information on furanone, a well acknowledged scaffold, to help scientists to develop novel and new furanone based therapeutic agents at a faster pace. This updated review highlights the worth of numerous therapeutically active furanone based compounds developed by the medicinal chemists. SAR studies have also been derived which may be useful for rational designing of furanone derivatives with improved therapeutic index.