Medicinal Chemistry

Chronic Myelogenous Leukemia (CML) is a myeloproliferative disorder characterized by the appearance of abnormal proliferation of white blood cells in the Philadelphia chromosome. Current drugs target ABL kinase may have resistance or have risks of serious side effects. We performed molecular docking and 2D-QSAR modeling regarding ABL and its mutant T315I to discover the potential candidate compounds for CML treatment. We present four potent TCM compounds, salvianolic acid C, baicalin, 1,4-dicaffeoylquinic acid, and dihydroisotanshinone I as potential candidates as lead drugs from the TCM compounds. It might have the potential to treat Chronic Myelogenous Leukemia with fewer side effects.

A series of novel 6-amino-2-aryl-3H-indolone-N-oxides were synthesized at yields of up to 65% and characterized; one was further characterized using X-ray crystallographic analysis. Synthesized compounds were evaluated for their in vitro activity against a chloroquine-resistant (FcB1) strain of Plasmodium falciparum, as well as for the 50% cytotoxic concentration (CC50) on Vero cell lines. The most promising activities were observed for the fluorinated compounds, the most active in vitro being 6-(2-morpholinoacetamido)-2-(4-(trifluoromethoxy) phenyl)-3H-indolone-N-oxide (IC50: 15.5 nM). In addition, these compounds showed weak cytotoxicity leading to selectivity index values of >170, thus warranting further in vitro and in vivo studies.

The incentive of the present work has been primarily directed towards the design and synthesis of some novel pyrido[1,2-a]benzimidazoles with specific functionalities believed to have alkylation ability. This combination of pharmacological agents may enable synergistic anticancer effect. Nine compounds 5b, 13a, 13d, 13e, 14b, 14c, 15, 16, and 17 were selected by the National Cancer Institute (NCI), Bethseda, Maryland, USA to be evaluated for their in vitro antitumor activity. All the selected compounds were tested initially at a single dose (10 μM) in the full NCI 60 cell panel including leukemia, non-small cell lung, colon, CNS, melanoma, ovarian, renal, prostate and breast cancer cell lines. Majority of the test compounds exhibited moderate cytotoxic activity. The highest activity in all the investigated cancer cells was displayed by 14c against melanoma SK-MEL-5 cell line. This may be due to the impact of the lipophilic trifluoromethyl substitution on the biological activity profile.

Beta amino acids are the important macromolecules on earth and building blocks. They play key role in biological systems of living organisms. They are utilized as a part of arrangement for the most part pharmaceuticals. They have huge part in human science. They have pharmaceutical properties like as hypoglycaemic, antiketogenic, antibacterial properties, antifungal exercises and powerful insecticidal properties. They have pharmaceutical applications as they are utilized to get ready pharmaceutical items and agrochemical target atoms. Not just them, but their derivatives also play significant roles in different systems of organismal bodies. They also act as essential enzymes in humans as well as in animals. So, this review explores the scope of Beta amino acids.

Though halophytes are naturally adapted to salinity, their salt-tolerance limits are greatly influenced by endogenous (that is, physiological development stages) and exogenous factors (that is, salinity). In this work, the evaluation of oxidative stress, bioactive molecules contents, antioxidant activities and two enzymes involved in the synthesis of secondary metabolites were assessed in the edible halophytic species Cakile maritima as function of salinity (0, 100, 400 mM NaCl) and two physiological stages. Total phenols, flavonoids and tannin contents increased by 58, 80 and 18% in vegetative period and by 27, 28 and 31% in flowering one at 400 mM NaCl, respectively as compared to C. maritima shoots control. These data indicated that phenolic compounds played an important role in protecting this species from salinity. The stimulatory effect of the salt on the total phenols content leads to the investigation of the role of two regulatory shikimate/phenylpropanoid pathway enzymes in phenolic synthesis. Results indicated that increased treatment progressively stimulated positively the activities of phenylalanine ammonia lyase and shikimate kinase in the vegetative and flowering period. Increasing salinity is correlated to the accumulation of carotenoids, anthocyanin, proline and ascorbate contents. The antioxidant activity enhanced at the vegetative stage in salt condition as compared to the flowering one. These results strongly indicate that salinity induces the accumulation of secondary metabolites in C. maritima shoots by altering the phenolic synthesis enzymes, as well as for the up-regulation of antioxidant molecules defense.

The great genetic biodiversity of medicinal plants found in Egypt played an important role in the use of Egyptian herbal medicines throughout the years. The ancient Egyptians, used them in therapy protocols, which were clarified in their papyri and tombs walls; and passing by the modern prescriptions, trends were found for using traditional alternatives to costly medications, either alone or as supplements accompanying the chemical drugs in the treatment protocols. Though many challenges are found in Egypt for herbal medicine industry and marketing, as lack of scientific evidence, quality standards, marketing strategies, extensive documentation to protect intellectual property and post-harvesting technologies; yet good agriculture practice, proper marketing plans, and modern molecular technologies can help the efficient use of those medicinal plants and their exportation worldwide, fetching a high income source to Egypt for carrying out more scientific research in agriculture and developing green technologies to produce pollution-free medicinal plants.