Design, Synthesis, In Vivo, and In Silico Evaluation of Benzothiazoles Bearing a 1,3,4-Oxadiazole Moiety as New Antiepileptic Agents.

In the presented manuscript, a new series of 2-[4-methoxy-3-(5-substituted phenyl-[1,3,4]oxadiazol-2-ylmethoxy)-phenyl]-benzothiazoles (6a-n) have been synthesized and studied in vivo and in silico for their anticonvulsant potential. Maximum electroshocks (MES) and subcutaneous pentylenetetrazol (scPTZ) models have been used for in vivo anticonvulsant activity. Auto Dock 4.2 software was used for in silico studies, and the targeted protein was 5IOV.sThe antidepressant activity of selected compounds (most active) was determined as a reduction in locomotor activity through an actophotometer. In vivo and In silico studies proved that among all the synthesized compounds, 6f, 6h, 6j, and 6l were the most potent with no neurotoxicity as compared to conventional drugs (phenytoin and phenobarbital). The in silico studies also indicated about different binding interactions of synthetic compounds to localize the binding receptors. The most likely mode of action for these drugs, according to the docking analysis of active compounds with various targets, is their binding to the VGCC and NMDA receptors.

Insight into the Synthesis, Biological Activity, and Structure-activity Relationship of Benzothiazole and Benzothiazole-hydrazone Derivatives: A Comprehensive Review.

Heterocyclic compounds constitute the most important part of medicinal as well as organic chemistry. Most of the marketed drugs possess therapeutic activity because of the presence of heterocyclic scaffolds as part of their structure. A slight change in the structure of the heterocyclic moieties may result in a major change in the therapeutic response of the drug candidate. Among all heterocycle compounds, the compounds containing nitrogen and sulfur atoms serve as a unique resource for drug development, such as benzothiazoles. Benzothiazole is a benzofused heterocyclic that is widely reported as a constituent of naturally occurring chemicals and chiefly responsible for their pharmacological potential. It was also reported that the pharmacological activity of BTA may also be influenced by its coupling with aldehydes, ketones, or hydrazines to form respected benzothiazole-hydrazone derivatives. The present comprehensive review consists of various synthesis methods, biological activities, and structure-activity relationships of and targets of benzothiazole and benzothiazole-hydrazone derivatives to provide a wide range of information to medicinal chemists for future research work.

Camphor and Menthol as Anticancer Agents: Synthesis, Structure-Activity Relationship and Interaction with Cancer Cell Lines.

Cancer is a type of human cell degenerative disease that has afflicted a large number of people for years. Cancer is caused due to the abnormal proliferation of cells in any part of the body. Most of the prescribed anticancer drugs are synthetic in nature and have been reported with enormous adverse effects. The researchers are very much enthusiastic about the use of natural compounds and their derivatives, which have been reported with less toxicity. Natural compounds have emerged as promising synergistic compounds with potential anticancer effects. In vitro anticancer activity of natural compounds with special reference to camphor and menthol has been investigated against different cancer cell lines. It has been found that camphor and menthol derivatives have potential cytotoxic activity. The present literature review outlines the various methods for the synthesis of camphor and menthol derivatives, which have potential cytotoxic activity. It highlights various cancer cell lines, which are the target of these camphor and menthol derivatives as ligands, along with structure-activity studies.

Recent Insights on Synthetic Methods and Pharmacological Potential in Relation with Structure of Benzothiazoles.

Benzothiazole is a bicyclic heterocyclic compound that contains benzene fused with 1, 3- thiazole ring. Several researches established the potential of benzothiazoles as important moiety in various adverse pharmacological conditions. Benzothiazole and its derivatives have been in use and marketed as anti-microbial, anti-inflammatory, anti-diabetic, anti-oxidant, anti-convulsant, antitumor, etc. The variations in pharmacological potentials of benzothiazole and its derivatives have been rational with their chemical structure. Nowadays, hybridization of two or more pharmacophores to synthesize a single molecule with potent pharmacological action is used. This helps to synergize pharmacological properties, make interaction possible with many targets, or minimize the adverse effects associated with them. Several synthetic approaches have been reported for benzothiazole and its derivatives. In this present review article, we focused on recently adopted synthetic approaches for the synthesis of the benzothiazole nucleus and its derivatives. The structure-activity relationship in relation to different pharmacological activities has also been highlighted to provide a good understanding to the researchers for future research on benzothiazoles.

Docetaxel, capecitabine and carboplatin in metastatic esophagogastric cancer: a phase II study.

PURPOSE: A Phase I investigation of docetaxel, carboplatin, and capecitabine at our institution demonstrated the safety and tolerability of this regimen in patients with metastatic esophagogastric cancer. The objectives of this Phase II study were to determine the response rate, toxicity, and survival for patients with metastatic esophagogastric cancer treated with this regimen. MATERIALS AND METHODS: Chemotherapy naïve patients with metastatic esophageal or gastric cancer received a regimen comprised of docetaxel 40 mg/m(2), days 1 and 8, carboplatin AUC = 2, Days 1 and 8, and capecitabine 2000 mg/m(2), Days 1-10 in 21-Day cycles. Patients were treated until disease progression or unacceptable toxicity. RESULTS: Twenty-five patients were treated with a median of 4 cycles of chemotherapy. Twelve of 25 patients (48 percent) had a Grade 3/4 toxicity. There were no Grade 4 nonhematologic toxicities, and 1 patient (4 percent) had neutropenic fever. There were 3 complete responses, and 9 partial responses, for an overall response rate of 48 percent. The median survival was 8 months (95% confidence interval, 5.5-13 months), and the 1-year survival was 36 percent. CONCLUSIONS: Weekly docetaxel and carboplatin with capecitabine was an easily administered outpatient regimen. The response rate and 1-year survival were similar to more complex regimens. Future trials may investigate the substitution of carboplatin with more active agents.

Paclitaxel poliglumex (PPX-Xyotax) and concurrent radiation for esophageal and gastric cancer: a phase I study.

OBJECTIVES: To determine the maximal tolerated dose (MTD) and dose limiting toxicities of poly(l-glutamic acid)-paclitaxel (PPX) and concurrent radiation (PPX/RT) for patients with esophageal and gastric cancer. METHODS: Patients with esophageal or gastric cancer receiving chemoradiation for loco-regional, adjuvant, or palliative intent were eligible. The initial dose of PPX was 40 mg/m2/wk, for 6 weeks with 50.4 Gy radiation. Dose levels were increased in increments of 10 mg/m2/wk of PPX. RESULTS: Twenty-one patients were enrolled over 5 dose levels. Sixteen patients had esophageal cancer and 5 had gastric cancer. Twelve patients received PPX/RT as definitive loco-regional therapy, 4 patients had undergone resection and received adjuvant PPX/RT, and 5 patients had metastatic disease and received PPX/RT for palliation of dysphagia. Dose limiting toxicities of gastritis, esophagitis, neutropenia, and dehydration developed in 3 of 4 patients treated at the 80 mg/m2 dose level. Four of 12 patients (33%) with loco-regional disease had a complete clinical response. CONCLUSIONS: The maximally tolerated dose of PPX with concurrent radiotherapy is 70 mg/m2/wk for patients with esophageal and gastric cancer.