الفهرس 
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Abstract
Cancer is the uncontrollable growth and spread of body cells. Cancer can arise in any of the billions of cells that comprise the human body.
Breast cancer research is an important public health and scientific priority. Every year, around 1.7 million people are killed by this devastating disease, demonstrating that not enough progress has been made in disease prevention. Breast cancer, the most common disease among women worldwide, is expected to rise rapidly in incidence and mortality rates during the next 5 to 10 years.
Lung cancer is classified into numerous distinct types based on its histology and clinical appearance. Adenocarcinoma is the most common type of lung cancer among those who have never smoked. According to histological type, prognosis, and therapeutic implications, the two primary subtypes of lung cancer are small-cell carcinoma and non-small-cell carcinoma.
Chemotherapy’s low success rate in treating advanced forms of cancer has led many to dismiss it as a viable cancer treatment option. As a result, most cancer treatments include palliative care. Cancer chemotherapy is also risky since anticancer medications might have undesirable side effects.
Neo-cryptolepine is obtained from the African shrub Cryptolepis sanguinolenta. It is frequently employed in the traditional medicine of a number of nations in Central and West Africa. Neo-cryptolepine, an indolo[2,3-b] quinoline alkaloid, has multiple biological actions, such as DNA binding and topoisomerase II inhibition. This chemical is not only cytotoxic, but also antifungal, antibacterial, and molluscicidal; it also has
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antiprotozoal properties, including antitrypanosome, leishmania, schistosome, and plasmodium activity.
The bioactivities of neo-cryptolepine have been linked to its capacity to bind to DNA and block topoisomerase II, albeit the mechanisms behind these effects are unknown. The cytotoxic and antimalarial effects of neo-cryptolepines have received the most attention in research. Increase the bioavailability and cytotoxic action of the chemical molecule. Cancer is a condition that causes uncontrolled cell multiplication and spread throughout the body. Cancer can develop from any of the human body’s billions of cells.
Breast cancer is a significant public health concern and research topic. The incidence of this deadly disease remains disturbingly high, with around 1.7 million new cases reported each year; these rates suggest insufficient disease preventive advances. Incidence and mortality rates for breast cancer are projected to increase considerably over the next 5 to 10 years. Breast cancer is the most prevalent form of cancer among women worldwide.
Lung cancer is a diverse disease with various pathological and clinically important subgroups. Adenocarcinoma, on the other hand, is the most common subtype among nonsmokers. According to their core histological nature, prognosis, and treatment implications, small-cell carcinoma and non-small-cell carcinoma are the two primary subtypes of lung cancer.
Chemotherapy is currently regarded as an inefficient cancer treatment due to its uncommon success against advanced cancers. As a result, most of the cancer chemotherapy is considered palliative.
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Furthermore, cancer treatment is risky since anticancer medications have significant side effects.
The nitrogen tetracyclic heterocycle neo-cryptolepine was identified in Cryptolepis sanguinolenta, an African vine. It is frequently employed in traditional African medicine in a number of Central and West African nations. Neo-cryptolepine belongs to the small family of indolo[2,3-b] quinoline alkaloids and has a variety of biological functions, including DNA binding and topoisomerase II inhibition. In addition to being cytotoxic, antifungal, antibacterial, and molluscicide, this compound is antiprotozoal, specifically antitrypanosomal, antileishmanial, antischistosomal, and antiplasmodial.
Some of neo-cryptolepine’s bioactivities have been linked to its capacity to bind to DNA and block topoisomerase II, albeit the processes underlying these activities have yet to be investigated. The majority of neo-cryptolepine research has focused on its cytotoxic and antimalarial effects. To increase the organic chemical’s cytotoxic efficacy, its bioavailability and activity must be improved.
Study methodology: The present study used 11-chloroneocryptolpine 1 and 4,4-diamino-diphenyl-methane for preparation of 11-(4-Aminobenzylphenylamino) Neo-cryptolepine (BAPN). Also, the characterization was done by 1H-NMR, molecular docking experiments with MOE to determine its affinity to caspase 3, and the pharmacokinetics and oral bioavailability of BAPN were investigated using Swiss ADME data for Insilco and Insilco data for BAPN.
The cytotoxic effect of BAPN was tested in vitro on MCF-7 and A549 cell line and concentration inhibition 50 (IC50) was evaluated. The
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cytotoxic activity of BAPN on MCF-7 and A549 cell lines was done by MTT assay at different concentrations 0μg/ml, 1.55 μg/ml (half IC50), 3.1 μg/ml (equal IC50), or 6.2 μg/ml (double IC50) on MCF-7 cell line and at concentrations varying from 0 μg/ml to 7.14 μg/ml (double IC50) on the A549 cell line for 24, 48, or 72 hours.
Also, ELISA Assay for measuring the expression of PCNA, Ki67, P53, VEGF, and Caspase-3 cellular proteins was done.
Results
The subsequent examination into neo-cryptolepine 112’s cytotoxicity and effects on the cell cycle was thoroughly reported. The addition of a methyl group at the C11 position of neo-cryptolepine by 113 DIMIQ significantly enhanced its anticancer activity.
In the FT-IR spectra, the (NH) absorption band was identified at 3359 cm-1, while the (CH) aromatic and (CH) aliphatic bands were found at 3026 cm-1 and 2813 cm-1, respectively, and (C=C Ar) was found at 1612 cm-1.
In addition, the (N-CH3) group of the neo-cryptolepine core was recorded at 4.21 ppm and the (Ph-CH2-Ph) group was recorded at 4.36 ppm in the 1H-NMR spectrum, whereas the (N-CH3) group was recorded at 34.24 ppm and the (Ph-CH2-Ph) group was recorded at 35.29 ppm in the 13C-NMR spectrum.
Caspase 3 PDB: 7JL7 binding affinity was -7.126 and the RMSD was 1.842 °A.
The docking data for the BAPN in the caspase 3 pdb file 7JL7, the type of chemical bond, the amino acids involved in
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the interaction, the binding affinity values, and the root mean square deviation are displayed (RMSD).
BAPN dramatically boosted casepase-3 and P53 protein expression in MCF-7 and A549 cell lines as compared to cells treated with DMSO as a control.
BAPN therapy dramatically reduced VEGF protein release into the medium of MCF-7 and A549 cell lines. Furthermore, as compared to control cells, it significantly reduced PCNA and Ki67 protein expression in MCF-7 and A549 cell lines.