SYNTHESIS AND IN-VITRO ANTIPROLIFERATIVE ACTIVITY OF 2, 3-ARYL SUBSTITUTED 1, 3-BENZOXAZIN-4-ONE DERIVATIVES

Objective: The aim of the present work was to design and synthesize 2, 3-aryl substituted 1, 3-benzoxazin-4-one derivatives and evaluate them for in-vitro antiproliferative activity against human breast adeno-carcinoma cells. Methods: The compounds were synthesized and screened for in-vitro antiproliferative activity against MCF-7 cell lines using 96 well plate method. Results: 3 out of 9 synthesized compounds showed good in-vitro inhibition of MCF-7 cell lines. Compound 2 showed least IC50 (highest active) i.e. 0.89 µg followed by compound 4 (IC50= 1.02 µg) and compound 3 (IC50= 1.19 µg). 4 compounds showed more than 90 % inhibition at 100 µg after 48 h incubation. Conclusion: This class of compounds showed some initial promising activity which can be further expanded by synthesizing and testing more analogs of this kind against MCF-7 cell lines which may give good leads to proceed

Pharmacognostic evaluation and antibacterial activity of dry fruits of Piper attenuatum buch-ham

Objective: The aim of the present work was to perform complete pharmacognostic evaluation of Piper attenuatum. Antibacterial activity was performed to explore the possible inhibitory property of dry fruit extract of Piper attenuatum against different microorganisms. Methods: Extensive pharmacognostic evaluation of dry fruits of P. attenuatum was performed which includes morphology, microscopy, phytochemical screening, physicochemical parameters (loss on drying, extractive values, ash values and pH) and high performance thin layer chromatography (HPTLC) profile. We also performed antibacterial activity for methanol, ethanol and ethyl acetate extracts of dry fruit powder of P. attenuatum by agar diffusion method. Results: The morphology of fruits of P. attenuatum was found similar to that of Piper nigrum with less folding on the fruits of P. attenuatum. The fruits have bland taste unlike the dry fruits of P. nigrum which are pungent. Powder microscopy showed the presence of different cellular structures. Phytochemical screening tests revealed the presence of different chemical constituents like alkaloids, tannins, carbohydrates, steroids and volatile oil. The HPTLC profile of crude sample showed many spots indicating its chemical diversity. Conclusion: All these tests gave the valuable data which may be helpful for its qualitative identification and further study. Antibacterial activity did not show prominent inhibitory property except at higher concentrations in methanol extract

Synthesis and in-vitro antiproliferative activity of 2, 3-aryl substituted 1, 3-benzoxazin-4-one derivatives

Objective: The aim of the present work was to design and synthesize 2, 3-aryl substituted 1, 3-benzoxazin-4-one derivatives and evaluate them for in-vitro antiproliferative activity against human breast adeno-carcinoma cells. Methods: The compounds were synthesized and screened for in-vitro antiproliferative activity against MCF-7 cell lines using 96 well plate method. Results: 3 out of 9 synthesized compounds showed good in-vitro inhibition of MCF-7 cell lines. Compound 2 showed least IC (highest active) i.e. 0.89 μg followed by compound 4 (IC= 1.02 μg) and compound 3 (IC = 1.19 μg). 4 compounds showed more than 90 % inhibition at 100 μg after 48 h incubation. Conclusion: This class of compounds showed some initial promising activity, which can be further expanded by synthesizing and testing more analogs of this kind against MCF-7 cell lines which may give good leads to proceed

Introduction, phytochemistry, traditional uses and biological activity of genus Piper: a review

Piper, the pepper plants or pepper vines are an economically and ecologically important genus in the family Piperaceae. It contains about 1,000-2,000 species of shrubs, herbs, and lianas, many of which are keystone species in their native habitat. Piper species have a pan tropical distribution, and are most commonly found in the understory of lowland tropical rainforests, but can also occur in clearings and in higher elevation life zones such as cloud forests. Most Piper species are either herbaceous or vines; some grow as shrubs or almost as small trees. Many species of piper have been used for treating different diseases in many traditions. E.g P. cubeba has been used in folk medicine, herbalism as well as in the early 20th century, as a cigarette flavoring. P. darienense is used medically by the Kuna people of the Panama-Colombia border region, and elsewhere it is used to intoxicate fish which then can be easily caught. Black Pepper (P. nigrum) essential oil is sometimes used in herbalism, and Long Pepper (P. longum) is similarly employed in Ayurveda, where it was an ingredient of Triphala Guggulu and (together with Black Pepper) of Trikatu pills, used for rasayana (rejuvenating and detoxifying) purposes

Synthesis and in vitro cholesteryl ester transfer protein inhibitory activity of novel esters of 2, 10-dichloro-12H-dibenzo [d,g] 1,3-dioxocin-6-carboxylic acid

Novel ester derivatives of 2, 10-dichloro-12H-dibenzo [d,g] 1,3 dioxocin-6-carboxylic acid were synthesized and evaluated for their in vitro human cholesteryl ester transfer protein (CETP) inhibition. Three out of twelve synthesized compounds showed good inhibition of CETP (more than 50%). Compound 10 showed 81.32% inhibition of CETP at the dose of 0.5 nM whereas compound 11 showed 75.78% inhibition when tested at the same concentration. Compound 8 and 13 also showed modest activity with 57.44 and 38.02% inhibition. All other synthesized compounds were devoid of significant inhibitory activity against CETP. We also performed molecular docking to predict the mode of binding of all compounds at the active site of CETP. Compound 10 showed the dock score of -9.16 whereas the dock score of compound 11 was found to be -9.09

Ultrasound-based approach to spiro-2,3-dihydroquinazolin-4(1H)-ones: their in vitro evaluation against chorismate mutase

Amberlyst-15 has been identified as a green and reusable catalyst in the synthesis of spiro 2,3-dihydroquinazolin-4(1H)-ones under ultrasound irradiation at room temperature. The reaction can be performed in an open flask as the conversion was found to be not sensitive to the presence of air or atmospheric moisture. The methodology was found to be general and a wide variety of spiro 2,3-dihydroquinazolin-4(1H)-ones were prepared from 2-aminobenzamides and cyclic ketones within a few minutes in quantitative yields. The products isolated do not require any chromatographic purification. This method provides advantages such as shorter reaction time, high yields of products, and simple operational procedures. Some of the compounds showed chorismate mutase inhibitory properties when tested in vitro

AlCl3 induced C–N bond formation followed by Pd/C–Cu mediated coupling–cyclization strategy: synthesis of pyrrolo[2,3-b]quinoxalines as anticancer agents

AlCl facilitated C-N bond forming reaction between 2,3-dichloroquinoxaline and anilines affording a convenient method for the preparation of N-aryl substituted 3-chloroquinoxalin-2-amines. A related N-benzyl derivative, however, was prepared via a conventional method. These N-alkyl/aryl substituted 3-chloroquinoxalin-2-amines on coupling with terminal alkynes in toluene under Pd/C-Cu catalysis afforded a range of 1,2-disubstituted pyrrolo[2,3-b]quinoxalines within 3-5 h in good to excellent yields. Some of the compounds synthesized showed promising anti-proliferative properties when tested in vitro against two cancer cell lines. Docking studies indicated that these molecules interact well with human Akt in silico

C-N bond formation under Cu-catalysis: synthesis and in vitro evaluation of N-aryl substituted thieno[2,3-d]pyrimidin-4(3H)-ones against chorismate mutase

A series of novel N-aryl substituted thieno[2,3-d]pyrimidin-4(3H)-ones were designed and synthesized as potential inhibitors of chorismate mutase. Synthesis of this class of compounds was carried out by using Cu-mediated C-N bond forming reaction between thieno[2,3-d]pyrimidin-4(3H)-ones and aryl boronic acids. The reaction can be performed in an open flask as the conversion was found to be not sensitive to the presence of air or atmospheric moisture. A range of compounds were prepared by using this method and single crystal X-ray diffraction study was performed using a representative compound. In vitro pharmacological data of some of the compounds synthesized along with dose response studies using active molecules are presented. In silico interactions of these molecules with chorismate mutase are also presented