Indole based prostate cancer agents

2022 ◽  
Vol 0 (0) ◽  
Author(s):  
Sunil Kumar ◽  
Madhuri T. Patil ◽  
Deepak B. Salunke

Abstract Cancer weakens the immune system which fails to fight against the rapidly growing cells. Among the various types of cancers, prostate cancer (PCa) is causing greater number of deaths in men after lung cancer, demanding advancement to prevent, detect and treat PCa. Several small molecule heterocycles and few peptides are being used as oncological drugs targeting PCa. Heterocycles are playing crucial role in the development of novel cancer chemotherapeutics as well as immunotherapeutics. Indole skeleton, being a privileged structure has been extensively used for the discovery of novel anticancer agents and the application of indole derivatives against breast cancer is well documented. The present article highlights the usefulness of indole linked heterocyclic compounds as well as the fused indole derivatives against prostate cancer.

RSC Advances ◽  
2019 ◽  
Vol 9 (32) ◽  
pp. 18670-18677 ◽  
Author(s):  
Venkata Rao Ghanta ◽  
Nagaraju Madala ◽  
Aparna Pasula ◽  
Sai Kiran S. S. Pindiprolu ◽  
Kumara Swamy Battula ◽  
...  

In the present study, novel dermacozine-1-carboxamides (8a–8n) were synthesized and screened for their in vitro cytotoxic activity against three different cancer cell lines: MCF-7 (breast cancer), A-549 (lung cancer) and DU145 (prostate cancer).


2021 ◽  
Vol 33 (10) ◽  
pp. 2327-2332
Author(s):  
Manoj Kumar Mandadi ◽  
Ramana Reddy Bobbala ◽  
Balakrishna Kolli ◽  
Rambabu Gundla

A series of novel amide tagged trifluoromethyl indole and pyrimido indole derivatives 4a-e & 5a-e and 6a-d & 7a-d were synthesized from 4-methyl-2-(methylamino)-6-(trifluoromethyl)isophthalonitrile (1) on reaction with bromoethyl acetate to obtain 2a and 2b isomers. Compound 2a treated with hydrazine hydrate followed by Schiff base reaction to get compounds 4a-e. In another way, compound 2a on reaction with aliphatic primary amine to get compounds 6a-d. For cyclization, compounds 4a-e & 6a-d treated with trifluoroacetic acid to obtain compounds 5a-e and 7a-d, respectively. All the synthesized compounds 4a-e & 5a-e and 6a-d & 7a-d were tested for anticancer activity against four human cancer cell lines such as A549-lung cancer (CCL-185), MCF7-breast cancer (HTB-22), DU145-prostate cancer (HTB-81) and HeLa-cervical cancer (CCL-2). Compounds 9e and 9f were found to have promising anticancer activity at micromolar concentration.


2022 ◽  
Vol 12 ◽  
Author(s):  
Sicon Mitra ◽  
Uttpal Anand ◽  
Niraj Kumar Jha ◽  
Mahipal S. Shekhawat ◽  
Suchismita Chatterjee Saha ◽  
...  

Piperine and piperidine are the two major alkaloids extracted from black pepper (Piper nigrum); piperidine is a heterocyclic moiety that has the molecular formula (CH2)5NH. Over the years, many therapeutic properties including anticancer potential of these two compounds have been observed. Piperine has therapeutic potential against cancers such as breast cancer, ovarian cancer, gastric cancer, gliomal cancer, lung cancer, oral squamous, chronic pancreatitis, prostate cancer, rectal cancer, cervical cancer, and leukemia. Whereas, piperidine acts as a potential clinical agent against cancers, such as breast cancer, prostate cancer, colon cancer, lung cancer, and ovarian cancer, when treated alone or in combination with some novel drugs. Several crucial signalling pathways essential for the establishment of cancers such as STAT-3, NF-κB, PI3k/Aκt, JNK/p38-MAPK, TGF-ß/SMAD, Smac/DIABLO, p-IκB etc., are regulated by these two phytochemicals. Both of these phytochemicals lead to inhibition of cell migration and help in cell cycle arrest to inhibit survivability of cancer cells. The current review highlights the pharmaceutical relevance of both piperine and piperidine against different types of cancers.


2006 ◽  
Vol 24 (18_suppl) ◽  
pp. 13029-13029
Author(s):  
E. Gallerani ◽  
S. Cresta ◽  
D. Tosi ◽  
C. Sessa ◽  
G. Capri ◽  
...  

13029 Background: Proteasome inhibition blocks the chemotherapy-induced activation of NF-кB increasing chemosensitivity to anticancer agents due to increased apoptosis. NF-кB is frequently aberrantly activated in primary human carcinomas and over-expressed in aggressive breast cancer lines1 supporting the rationale for combining B with P. We designed a phase I-II and PD trial to determine the recommended dose (RD) of the B&P combination, to screen for antitumor activity in patients with potentially taxane-sensitive tumors, to search for drug-induced changes and to identify potential surrogate markers of drug activity and toxicity in peripheral blood mononuclear cells (PBMC). Methods: Eligibility included ECOG performance status < 2, neurotoxicity < 2 and adequate organ functions. Treatment was given Q21 days: B on days 1,4, 8 and 11 and P on days 1 and 8. PBMC for gene expression profiling have been collected on day 1 and 4 before and after therapy. RECIST for response was applied. Results: Twenty-nine patients (20 female, median age 60 yrs) were accrued and 25 are evaluable (breast cancer: 13, ovarian cancer: 7, prostate cancer 1, other 4) ; 16 pts were treated in 4 escalation levels and the RD defined respectively at 1.3 mg/m2/dose & 100 mg/m2/dose for B&P. Neurotoxicity was the main toxicity (G1 36%, G2 20% and 1 case G3) requiring treatment discontinuation in 2 pts at cy 6 & 7. Other toxicities (all grades) were nausea and vomiting (68%), diarrhea (56%, G3 12%), alopecia (52%), asthenia (36%, G2 4%), and myalgia (32%, G2 8%). Antitumor activity consisted of 3 PR in pts with ovarian cancer lasting respectively 14, 8+ and 16 wks; 2 PRs in pts with breast cancer (12+ wks,14+ wks) and 1 PR in a pt with prostate cancer. Conclusions: Thus far the regimen has acceptable toxicity with evidence of antitumor activity. The trial will continue until accrual of four additional patients as planned. Footnotes 1 Adams J Current Opin Oncol 2002, 14:628–634. [Table: see text]


2006 ◽  
Vol 24 (18_suppl) ◽  
pp. 18597-18597
Author(s):  
Y. Rottenberg ◽  
T. Peretz

18597 Background: In industrial countries, the cancer burden of the elderly is high and is increased. One reason is longer life expectancy. Increasing age standardized rates of cancer in this age group compared to younger groups may also explain this phenomenon. Methods: Two age groups were examined, above and below 65 years. Each age group was further divided into men and women. The age standardized rates for all cancers combined among the Jewish population in Israel were identified through the Israel Cancer Registry during the years 1973–2002. In addition, lung and colorectal cancers according to sexes, prostate cancer in men and breast cancer in women were examined. Results: Between the first 5 years of the study (1973–1977) and the last 5 years (1998–2002) the age standardized rates for all cancers combined were raised by about one third in the two age groups. In males, the overall change was higher in the older group (42% in men aged 65 years and older compared to 31% in men younger than 65). However, the rise in the younger group was more prominent in females (42% in women younger than 65 years compared to 33 % in women aged 65 and older). The most outstanding increase was in prostate cancer in men, but mainly in the younger group (176% in the older group and 368% in the younger group) followed by breast cancer in women, more prominent in the older group (64% in the older group and 50% in the younger group). In both sexes, more noticeable increases were noted in the older groups in colorectal cancer and in lung cancer. Between the years 1993–1997 and 1998–2002 shifts towards stabilization and even a decrease was noted in some of the cancers that were examined. In men aged 65 years and older rates for all cancers combined were decreased by 2.5%, among the specific tumors and a decrease was noted in lung cancer (6.7%) and prostate cancer (5.8%). The rates for all cancers combined among the older women were slightly decreasing (2.0%). No decrease was noted in the specific tumors in this group. Among the younger groups in both sexes, no decrease (defined >0.5%) was noted. Conclusions: These data argue against the hypothesis that the overall change in the cancer burden in the aged could be also explained by differences changes in the risk of developing cancer between these two age groups. No significant financial relationships to disclose.


2012 ◽  
Vol 30 (15_suppl) ◽  
pp. 1502-1502
Author(s):  
Niloofar Taghizadeh ◽  
Judith M. Vonk ◽  
H. Marike Boezen

1502 Background: There are indications of an association between Body Mass Index (BMI) and risk of different cancer types. There is dispute whether this association differs between males and females. Methods: We studied the association of BMI at the first survey with risk of mortality from the most common types of cancer (lung, colorectal, breast and prostate cancer) in a large general population-based cohort study (Vlagtwedde-Vlaardingen, 1965-1990) with follow-up on mortality status until 2009. Additionally, we assessed this association based on tertiles of the annual change in BMI (defined as the difference between BMI at last survey and first survey divided by the time between last and first survey). We used 3 categories of BMI (< 25 kg/m2, 25-30 kg/m2, and ≥ 30 kg/m2) and changes in BMI (< 0.02 kg/m2/yr, 0.02-0.2 kg/m2/yr, and > 0.2 kg/m2/yr) in the analyses. The multivariate Cox regression model was adjusted for age, smoking, gender. Analyses were additionally stratified by gender and smoking. Results: Among all 8645 subjects, 1194 died due to cancer (lung cancer: 275; colorectal cancer: 134; breast cancer: 117; prostate cancer: 83). Mortality from all types of cancer was significantly increased in subjects with BMI > 30 kg/m2 (HR (95 % CI)) = 1.22 (1.00-1.48)), especially in females (1.38 (1.06-1.81)) and in never smokers (1.39 (1.02-1.90)). Prostate cancer mortality was significantly increased in males with BMI 25-30 kg/m2 (2.04 (1.90-3.83)) and > 30 kg/m2 (2.61 (1.02-6.67)). This association between prostate cancer mortality and BMI was higher in smokers. Lung cancer mortality risk was decreased in subjects with BMI 25-30 kg/m2 (0.71 (0.54-0.93)) and > 30 kg/m2 (0.82 (0.50-1.32)), especially in males, in smokers, and in smoking males. There were no significant associations between BMI and colorectal or breast cancer mortality nor between change in BMI and mortality from all analyzed types of cancer. Conclusions: We show that an increase in BMI is associated with an increased risk of mortality from all types of cancer in females and with an increased mortality risk from prostate cancer in males but with a decreased lung cancer mortality risk, especially in males. More research is needed into the biological mechanisms that link BMI to cancer.


2015 ◽  
Vol 33 (29_suppl) ◽  
pp. 186-186
Author(s):  
Florian Scotte ◽  
Alexandre Vainchtock ◽  
Nicolas Martelli ◽  
Isabelle Borget

186 Background: Cancer patients represent an at-risk population for Venous Thromboembolic Events (VTE). Our study aimed to evaluate the impact of VTE on the length and cost of hospital stay in French patients hospitalized for breast cancer (BC), colon cancer (CC), lung cancer (LC) or prostate cancer (PC). Methods: The French national hospital database (PMSI) and the disease-specific ICD-10 codes were used to identify BC, CC, LC or PC patients diagnosed in 2010 who were hospitalized with a VTE during the following two years. We selected stays during which a VTE occurred but was not the main reason of hospitalization (cancer was classified as primary/related diagnosis and VTE as significant associated diagnosis). Those stays were matched and compared to similar stays (same cancer and same reason for hospitalization) without VTE. Costs were calculated using the French official tariffs, from the perspective of the third-party payer. Results: We identified 214 stays for breast cancer during which a VTE occurred and was classified as significant associated diagnosis, 843 stays for colon cancer, 1301 for lung cancer, and 126 for prostate cancer. The comparison between those stays and similar stays without VTE showed significant increase of hospital stay duration in patients experiencing VTE. Median duration rose from 4 to 7 days in BC patients, from 8 to 16 days in CC, from 2 to 9 days in LC and from 6 to 10 days in PC. Consequently, the median expenditure per stay increased by 37% in BC patients with VTE (up to € 5,518), by 61% in CC (up to € 9,878), by 202% in LC (up to € 7,308) and by 22% in PC (up to € 6,200). Conclusions: When occurring during hospitalization, VTE made cancer management much heavier: patients faced prolonged hospital stays whereas healthcare system faced significant additional cost. Better prevention and follow-up measures could reduce this burden, and benefit both patients and hospitals. [Table: see text]


ESMO Open ◽  
2020 ◽  
Vol 5 (Suppl 4) ◽  
pp. e000796
Author(s):  
Nuria Mederos ◽  
Alex Friedlaender ◽  
Solange Peters ◽  
Alfredo Addeo

Lung cancer remains the leading cause of cancer-related deaths worldwide in women and men. In incidence, lung cancer ranks second, surpassed by breast cancer in women and prostate cancer in men. However, the historical differences in mortality and incidence rate between both sexes have changed in the last years. In the last decades, we have also witnessed an increased number of lung cancer in female never-smokers. These disparities have grown our interest in studying the impact of the gender and sex in the presentation of lung cancer. The aetiology is yet to be fully elucidated, but the data are clear so far: there is a growing divide between lung cancer presentation in women and men that will change our management and study of lung cancer. This article aims to review the sex and gender differences in lung cancer.


2001 ◽  
Vol 71 (3) ◽  
pp. 287-293 ◽  
Author(s):  
Cristina Al Matarneh ◽  
Catalina-Ionica Ciobanu ◽  
Violeta Mangalagiu ◽  
Gheorghita Zbancioc ◽  
Ramona Danac

We report herein a comparative study concerning the influence of microwave (MW) irradiation comparative with conventional thermal heating (TH) in the reaction of six member ring azaheterocycles (derived from phenanthroline, quinoline, isoquinoline and phthalazine) with ethyl cyanoformate, and their anticancer and antimycobacterial activity. Under MW irradiation the reactions have some undeniable advantages: the reaction times decrease dramatically (from hours to minutes), the yields are higher, the reactions became selective in some cases (4,7-phenanthrolinium and phthalazinium ylides). The decreasing of reaction time+ from hours to minutes corroborated with the fact that in majority of cases the yield are higher and the selectivity is better, allow us to say that these reactions could be considered as eco-friendly. As far for biological activity, three of the compounds exhibited a significant antitumor activity against some cancer cell lines including prostate cancer, leukemia, renal cancer, lung cancer and breast cancer. The best potency in terms of growth inhibition of tumor cells (~45%) was shown by compound 4a against renal cancer A498 and ovarian cancer SK-OV-3 cells. The tested compounds have not shown any antimycobacterial activity against Mycobacterium tuberculosis.


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