1. Introduction
The Pyrazoles were an important class of compounds, since they have been proven as, extremely useful intermediates in the synthesis of new biological targets. The pyrazole ring system was found to be a versatile component in numerous pharmacological and agro chemically important compounds, heterocycles with fused pyrazoles were known to contribute to various chemotherapeutic activities like, antimicrobial [1-9], free radical scavenging [10], anti-inflammatory [11-13], analgesic, antipyretic and antiviral [14-15]. The pyrazole derivatives were also reported as inhibitors of HIV-1 reverse transcriptase [16], sodium-hydrogen ion exchanger NHE-1[17], and dipeptidase IV (DPP-IV) inhibitors [18]. Several compounds of this type were found to function as antagonists of the αvβ3 receptors, which are present on the surface of many tumor cells [19], and insecticides in agro chemistry [20]. Several lines of evidence support the view that, chemotherapy has become one of the most significant treatment modalities in cancer management. Consequently, the principal obstacle to the clinical effectiveness of chemotherapy was based on its possible toxicity to normal tissues of the body, beside the development of cellular drug resistance especially to conventional anticancer agents [21, 22]. Over the past two decades, pyrazole-containing compounds have received considerable attention owing to their different chemotherapeutic potential including versatile anti-neoplastic activities. The literature survey revealed that some pyrazole was implemented as antileukemic [23-25], antitumor [26-29], and anti-proliferative agents [30, 31], besides their capability to exert remarkable anticancer effects through inhibiting different types of enzymes...
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3. Conclusion
In summary, a series of novel bis-pyrazoles with amides, sulfonamides (6a-o) and ureas (6p-t) were synthesized and subjected to DNA binding studies. The binding pattern was analyzed through an AUTODOCK server in that 6h showed lowest conformational energy than other compounds. Then all the above compounds were evaluated for their in vitro cytotoxicity against Panc-1 (human pancreatic adenocarcinoma), H460 (human non small cell lung carcinoma) cell lines by a WST-1 cytotoxicity assay. Among them, 6a and 6b were identified as lead molecules since both were exhibited promising activity towards both the cancer cell lines. The compounds 6k and 6l were found to exhibit the activity particularly towards the pancreatic cell line and hence continuing studies to substantiate and improve activity profiles are underway in our laboratory.
In addition to this, these compounds also display antagonist activity to calcium 23. For this reason, and for their associated pharmacological properties, a lot of interest and attention has been drawn to them in the recent years by researchers 22. A couple of methods have consequently been developed for the preparation of the octahydroquinazolinone derivatives 2. The most common of which include the Biginelli one pot reaction that involves urea/ thiourea, aromatic aldehydes and dimedone 24. Other methods include synthesis with the help of catalysts like concentrated sulfuric acid, Nafion-H, ionic liquid, and TMSCI 24. Synthesis in low ethanol could also be adopted but it is characterized with product yields that are between 19-69% and these are
accomplished the synthesis of non-toxic aminoalkyl substituted isonicotinyl hydrazide by Mannich reaction.[148][ref:] The Mannich products were found to be more active against several Gram-positive and Gram-negative bacteria. Karthikeyan et al. reported the synthesis and biological activity of 2,4-dichloro-5- fluorophenyl substituted Mannich base derivatives 27 (figure 8 ).[149][ref:] TheMannich base derivatives showed good antibacterial and antifungal
The well-known “penicillin of cancer drugs” is probably an appropriate nickname of cisplatin due to its world widely use as the first and one of the most effective treatment for numerous cancer diagnoses. One important thing that must be point out is that cisplatin is a very simple inorganic molecule comparing to other cancer drugs which generally are complex organic molecules. In order to design and develop new related cancer drugs, cisplatin has been used as a gold model by many scientists.
Chemotherapy is the treatment of a tumor with chemical agents to reduce mass or eradicate a tumor completely. There are certain mechanisms by which chemotherapy inhibits cancer. The first mechanism is cell death by cytotoxicity. Some chemical agents in certain amounts are toxic to cells. The cells die due to the toxic...
Histone acetylation and deacetylation are two ways to modify histones on chromosomes, thereby regulating genetic expressions. Butyrate was reported as a non-competitive, reversible histone deacetylases (HDAC) inhibitor [19-21], additionally other HDAC inhibitors, such as sodium valproate, sulforaphane, apcidin etc., were examined as the genetic expression promoters [22-25]. In our study, we determined the effects on HBD1 and LL-37 expression induced by seven HDAC inhibitors (Figure 4).
...ubstrate by non-perfectly conserved residues’ and by ‘the residues flanking the active-site region.’ This suggestion is consistent with the observation that two exosites are crucial for SNAP-25 binding to the LC of BoNT/A (Breidenbach and Brunger, 2004). The α- and ß-exosites were recognized as being potentially important in the development of specific inhibitory drugs, and targeting the peripheral sites of substrate binding has focused on a family of bis-imidazole inhibitors for BoNT/A (Merino et al., 2006). A recent study by Eubanks et al. (2007) has highlighted limitations of conventional drug development paradigms. The authors found that high-throughput screens did not consistently predict the candidates that would be most effective in their cell-based assays. Eubanks et al. (2007) also observed that efficacy in cell culture did not predict protection in vivo.
Many plants and plant derived products are used in cancer therapy as cytotoxic agents. Examples include Taxol that is used for breast cancer (which gets its active constituent from Pacific Yew tree) and the vinca alkaloids used for leukaemia (from the Madagascar ...
Gallagher et al. has established a library of compounds on 6-6 fused bicyclic pyridine. Here 2, 6-difluoropyridine 5.3 underwent nucleophilic substitution with 3-amino-1-propanol to provide 5.4 in 95% yield. It was mesylated and cyclized to give the pyridinium salt 5.5 and eventually mild basic hydrolysis of 5.5 furnished 5.6 in 85% yield (Scheme 5.2).32
The 1H NMR for p-acetotoluidide (Figure 1) contained five significant signals. Four of the signals were produced by p-acetotoluidide while the fifth signal (7.25 δ) was produced by the 1H NMR solvent, CDCl3. Due to proton exchange due to hydrogen bonding, there was no significant signal produced for the hydrogen bonded to the amide group. Due to this quality of hydrogen bonding the signal can manifest as broad, at the wrong chemical shift, or be absent. In this case, the signal produced by the hydrogen bonded to the amide group was absent. A list of the types of hydrogens and their chemical shifts for p-acetotoluidide was recorded (Table 2).
Cancer is one of the leading causes of death worldwide as it can develop in almost any organ or tissue. Significant advances in understanding the cellular basis of cancer and the underlying biological mechanisms of tumour has been vastly improved in the recent years (Jiang et al. 1994). Cancer is a genetic disease which requires series of mutation during cell division to develop, it has characteristics which can be associated with their ability to grow and divide abnormal cells uncontrollable while in the mean time invade and cause nearby blood vessels to serve its need. Even though many people are affected by cancer today, the abilities which cancer cells own make it hard to find single effective treatment for cancer. The focus of research now lies on developing drugs which target cancer cells in the hope to cure cancer once and for all.
Li, L., Zhu, Z., Joshi, B., Porter, A.T. and Tang, D.G. (1999) A novel hydroxamic acid compound, BMD188, demonstrates anti-prostate cancer effects by inducing apoptosis. I: In vitro studies. AntiCancer Res., 19, 51-60.
Guanidines. The cyclic thiourea compound had greater inhibiting in the lung cancer cells compared to the bis-cyclic Guanidines. these compounds decreased the mRNA of PTHrp and hence decreased their transcription. The results showed that the decrease in the levels pf PHTrp was not due to cytotoxcicity on the cells , however due to a decrease in the promoter reporter concstruct specifically the P3 promoter .(19)
The work to be presented in the thesis entitled “Synthesis of some novel (1, 3) benzothiazole heterocyclies for pharmacological screening” is divided into five chapters. Beginning with a chapter on introduction where in those feature of the past work have been highlighted which have inspiring us to undertake this study. A brief account of pharmacological and biological evaluation of the synthesized compound is given in chapter five. The main focus of this thesis is to prepare some potent compounds and screened them for biological evaluation by incorporation of azetidinone, thiazolidinones, and pyrazoline in benzothiazole nucleus. The idea behind formulating such a study was to access the favorable impact if any they produce on the biological activity in the new molecules through the additive or cumulative effect exercise by each of these moieties. If there role to produce a positive impact on activity was established, such structure were likely to form interesting targets in synthesis and biological evaluations. To test this hypoth...
Chemistry has lots of charming facts; one such is hetero cyclic compounds. Heterocyclic compounds are organic compounds that contain a ring structure containing atoms in addition to carbon, such as sulfur, oxygen or nitrogen as the heteroatom. The ring may be aromatic or non-aromatic. Every first step of life starts with hetero-cyclic compounds. Every man's potential to think, intelligence, behavior, character depends on his gene. The basic skeleton of the genetic material (DNA) is made up of heterocyclic compound like adenine, guanine, cytosine and thymine. Thus knowing about heterocyclic compound and its application is part of venturing human life. The different pharmacological activity of the different hetero cyclic compounds ring , from a last related to this moiety and screened them for their different pharmacological activities to get a molecule which have good pharmacological activity and lesser side effect. These pharmacological activities of new hetero cyclic derivatives this hetero cyclic has shown its importance as antibacterial, antifungal, anti-inflammatory, hypoglycemic, antidepressant, anti-malarial, analgesic, anticancer
The quinolinone and quinoline ring is highly prevalent in natural compounds. There are synthetic and potential agents, which show various pharmacological properties (Priya et al., 2012). Quinolinones are important structural intermediates for synthesis of functionalized quinolines (Baston et al., 2000). Quinolines have demonstrated various applications such as biomedical (Ridley et al., 2002), fungicides (Oliva et al., 2003), virucides (Liu et al., 1997), biocides (Sabatini et al., 2013), alkaloids (Fournet et al., 1993) rubber chemicals and flavoring agents (Jones et al., 1996). They